ABSTRACT
Background: The incidence of
head and neck squamous cell cancer is quite high in India as
compared to the developed countries. Conventional RT for the majority of
head
and neck cancers is delivered using two parallel opposed radiation beams and parotid glands
receive a significant radiation dose (>50 Gy) resulting in permanent
xerostomia.
Materials and Methods: For this study, we evaluated 64 patients with oral cavity and oropharyngeal squamous
cell carcinomas, treated by
IMRT / Conventional RT for xerostomia related quality of life (QoL). We
used EORTC H&N35 QLQ for analysis of data & divided the questions into
xerostomia experienced
at rest and during meals.
Results: Patients treated with IMRT reported significantly less difficulty in transporting and swallowing
their food and needed less water for a dry mouth during day, night and meals. Within the IMRT group the xerostomia
scores were better for those patients with mean parotid dose to the "spared" parotid < 26 Gy.
Discussion: The
parotids are responsible for the saliva output during meals whereas the oral
cavity and submandibular glands lubricate the mouth at rest. Our results showed that patients receiving IMRT had a
better
xerostomia related
QoL than patients who received bilateral opposed radiation
fields. Xerostomia at rest and during meals was used as the endpoint in our analysis.
Conclusion: Parotid gland sparing IMRT improves xerostomia related
QoL.
Keywords: Head and Neck Cancer, Xerostomia, IMRT, QoL
INTRODUCTION :
The incidence of
head and neck squamous cell cancer is
exceptionally high in India (over 30%) as compared to western and other developed countries (around 5%).
This is attributed to popular practice of chewing betel
nut leaves rolled with lime and tobacco (a mixture known as "Pan") which results in prolonged carcinogen
exposure to the oral mucosa. The practice of "Reverse Smoking" (smoking with the lighted end of the cigar in
the mouth, also known as Chutta), peculiar to certain parts of India, is associated with increase in cancer of
the hard palate. The
oral cavity bears the brunt of the carcinogen and nearly 80,000
oral
cancers are diagnosed
every year in the country. Nearly two thirds of these are located in the gingivo-buccal complex (comprising the
lower gingivum, buccal mucosa and retro-molar trigone), where the betel 'quid' is kept for long periods .In
head and neck cancer oral cavity comparises 9.4%
of all cancers and oropharynx comparises 6.9% of all cancers in india.
The majority of cases are
locoregionally advanced (Stage III & IV ) at the time of diagnosis. Our
centre being the largest Government Medical College in the
largest State of India, has high number of such patients.
Our centre has been accredited by
ESMO (European Society of Medical Oncologists) as an Integrative
Oncology and Palliative Care Centre.
Because of critical location of most of these neoplasms, they interfere with breathing, eating and phonation, thus
affecting the quality of life.
Surgery and/or
chemoradiotherapy are the mainstay of the
treatment of
locally advanced head and neck cancers.
Radiotherapy as the primary treatment option allows for
organ and function conservation. Unavailability of good
quality surgical facilities at every centre; high expenses
of surgery and newer IMRT techniques weighs heavily
in treatment decisions, with more patients preferring
conventional chemoradiotherapy. A large number of
patients are referred for primary radiation therapy,
irrespective of stage and probability of disease control.
Radiation-induced
xerostomia (dry mouth) is one of the
common complications of
head and neck irradiation.(3)
Radiation-induced salivary gland injury often occurs
because most of the salivary glands are included in the
general irradiation fields for head and neck malignancy
and regional lymph nodes. Salivary gland radiation
injury leads to salivary secretion dysfunction and
induces several clinical symptoms such as dysphagia
(swallowing difficulty) and xerostomia (with speech
difficulty, sleep disturbance, intraoral infection, and
dental caries(4) .There is reduction in salivary output
and change in salivary composition.
MATERIALS AND METHODS
Patients: All the patients had T 1-4, N 0-2, M 0 (Stage
III/IV) oral cavity or
oropharyngeal cancers (Table 2,3).
The primary tumor (site) received a total dose of 70 Gy
in 2 Gy daily fractions, 5 fractions a week, using
Conventional or IMRT techniques. 30 patients were
evaluated for xerostomia related quality of life - 15 each
in IMRT and Conventional (Control) arms.
Data Collection tool: Assessment of xerostomia
related quality of life
All patients completed the xerostomia related
questionnaire of EORTC QLQ-H&N35 [5] where
items are rated on a four-point scale. Higher scores
represent worse symptoms. The questionnaire was
translated for use in local language. This assessment
took place twelve months after radiotherapy treatment.
We divided the
QoL questions in 2 parts; the first part
concerned with questions on xerostomia experienced at
rest and the second part related to questions on
xerostomia experienced during meals (Table 3,4).
Treatment:
Irradiation was given on a
linear accelerator
( 6 MV Siemens Oncor Expression ) and all patients
were immobilized using custom made masks. IMRT was
delivered using the Linatech planning system; 95% of
the Planning Target Volume (PTV) had to receive 95%
of the prescribed dose. The aim was to reduce the mean
dose to 26 Gy or less for at least one parotid gland (Fig.
1). Sparing of the submandibular glands or oral cavity
was not attempted.
The Control group was irradiated with lateral- opposed
photon beams (
6 MV photons customized with MLC
shieldings). The maximum dose allowed to the spinal
cord was upto 50 Gy in both groups.
RESULTS
Patient characteristics: The mean dose to the primary
tumor was 70 Gy in both IMRT and the control groups
(Table 1, 2). The patients received platinum based
chemotherapy concurrently. No salivary stimulating or
protective agents such as
pilocarpine or amifostine were
allowed during the study.
Table 1: Patient Demographics
Age ( years )
IMRT (%)
Control
(%)
20 � 30
2 (6)
1 (3)
30 - 40
4 (13)
5 (16)
40 - 50
8 (25)
9 (28)
50 - 60
10 (31)
11 (34)
60 - 70
8 (25)
6 (19)
Total
32
32
Table 2: Patient Characteristics
Sex
IMRT (%)
Control (%)
Males
25
(78)
27(84)
Females
7 (22)
5(16)
Tumour Site
Oral Cavity
17 (53)
16(50)
Oropharynx
15 (47)
16(50)
T - stage
T1
7 (22)
12(38)
T2
10 (31)
15(47)
T3
12 (38)
3(9)
T4
3 (9)
2(6)
N - stage
N0
15 (47)
11(34)
N1
15 (47)
16(50)
N2
2 (6)
5(16)
Mean dose primary tumour (Gy) 70
70
Concomitant chemotherapy
Yes
Yes
Xerostomia in rest:
Patients on IMRT were examined extensively regarding complaints related to xerostomia
and almost all the complaints in the questionnaire were
reported less frequently in the
IMRT group (Table 3).
Patients who received IMRT needed to drink water less
often during the day. They did not experience a dry
mouth as often and speaking was less impaired due to a
dry mouth. No statistically significant difference in
insomnia complaints was reported due to a dry mouth.
Figure 1: IMRT plan demonstrating left parotid gland
sparing.
CTV1 - primary tumour and high risk nodes.
CTV2 � nodes at risk of micrometastases.
(CTV : Clinical Target Volume)
Xerostomia during meals: Again almost all
complaints were reported less frequently in the IMRT
group(Table 4). Patients who received IMRT reported
less difficulty in oral transport and swallowing of solid
and grounded food. They choked less often when swallowing.
Both groups of patients reported they needed to
swallow more often than before radiotherapy. No
statistically significant difference in swallowing liquid
food was reported.
Table 3: Questions related to xerostomia at rest
Table 4: Questions related to xerostomia at meals
DISCUSSION
Permanent
xerostomia is the most prevalent late consequence of irradiation of head and neck cancer and
a major cause of reduced quality of life (
QOL) [6]. In addition to perception of dryness, diminished salivary
output has other effects, like making mastication and deglutition difficult, which may contribute to nutritional
deficiencies, predisposing the patient to
mucosal fissures and ulcerations, changing the composition
of oral flora, promoting dental caries and contributing to
osteoradionecrosis [7].
The prevalence of xerostomia after radiotherapy of
head and neck cancer relates to the extreme
radiosensitivity of the salivary glands, with salivary acinar cell apoptosis at low doses and necrosis at high doses
[8].
In traditional
(2-dimensional) radiotherapy of
head and neck cancer, the placement of
the radiation fields and their shapes are based on the bony anatomy acquired by the simulator diagnostic-quality
films. These fields typically encompass large majority of all the salivary glands when advanced cancer is
irradiated. Using IMRT, the desired target doses can be delivered with a high
conformity, and dose limits to critical noninvolved organs are achieved at a higher degree than was
previously possible. In treating advanced head and neck cancer with highly conformal RT, an important goal has been
the sparing of the parotid glands to reduce xerostomia. IMRT reduces the radiation dose to the
contralateral
parotid gland to 32% compared to 93% for the standard plans.
In certain tumour sites like the base of tongue, it is essential to treat the
parapharyngeal spaces
bilaterally. In these patients it is still possible to spare the superficial lobes of the parotid glands on both
sides. The rationale behind this is that the parotid glands have their functional subunits organised in parallel ie.
damage to a part of organ does not result in complete loss of function.
The parotid glands are said to be largely responsible for the saliva output during meals whereas the
oral cavity
and submandibular glands are supposed to be mainly responsible for lubrication at rest [9].
Earlier reports on
QoL after
salivary gland sparing IMRT, except for Jabbari et al, made no
distinction in QoL during meals and during rest. In general: the differences between the conventional and the IMRT
group emerged largest and most significant by the xerostomia during meals questions [10,11,12].
We did this study to find out whether extra expenditure on newer radiation delivery techniques like IMRT will result
in favourable outcome with better quality if life especially in long term survivors. Our results showed that
patients receiving IMRT had a better xerostomia related QoL than patients who received bilateral opposed
conventional radiation fields. The aim of our treatment was to spare (one of) the parotid glands i.e. reducing the
mean parotid dose to below 26 Gy. Sparing of the
submandibular glands and oral cavity was not an
objective since this could not be achieved
together with irradiation of level II on both sides.
CONCLUSION
Compared to conventionally irradiated head and neck cancer patients, IMRT treated patients had improved xerostomia
related QoL during meals and in rest. Within the IMRT group the xerostomia scores were better for those patients
with a mean parotid gland dose to the "spared" parotid gland below 26 Gy [13,14].
The findings suggest that the development of new radiation delivery techniques like IMRT can significantly improve
these morbidities and thus the quality of life.
