radiotherapy (EBRT) causes
irreversible salivary dysfunction in
many patients treated for head and
neck cancer. One strategy for reducing
is to get a dental consult to
prepare the patient before beginning
strategy, now in clinical trials, is
to add cytoprotection with amifostine
(Ethyol) to the treatment
regimen. Both approaches were
discussed by Jonathan A. Ship,
DMD, professor, Department of
Oral Medicine, and director, Bluestone
Center for Clinical Research,
NYU College of Dentistry.
Oral Effects of Tx Significant
"Head and neck cancers cause
more deaths annually than malignant
melanoma, Hodgkin's disease,
and cervical cancer," Dr. Ship
said. "Survival rates are poor, with
only 50% of patients living 5 years
after diagnosis, and all treatments
have adverse sequelae. The severe
dental and oral effects are often
neglected in the rush to multimodality
therapy" (see Table 1).
Mucositis can be dose-limiting
and volume-limiting in combined
Dr. Ship said.
He also noted that mucositis is
a portal of entry for oral microorganisms,
leading to potentially
life-threatening secondary local
and systemic infections.
Dental Consult Recommended
"Patients need to see a dentist
prior to head-neck radiotherapy.
develops 7 to 10 days after treatment
initiation," he said.
He added that there is an incorrect
but widespread assumption
that dental care would not be reimbursed
by Medicare. "Certain
procedures in preparing the mouth
prior to head-neck radiotherapy
are covered by Medicare. This can
decrease pain and improve quality
Serous salivary glands such as
the parotid, he explained, are highly
radiosensitive, and serous cells
are destroyed within 1 to 6 hours
after irradiation with single doses
as low as 200 cGy. Noting that cancer
treatment doses are being
pushed to 65 to 70 Gy, he said a
dose of only 25 to 30 Gy can permanently
destroy major salivary
"The radiation sequela of salivary
dysfunction remains a bothersome
problem for patients who
have received EBRT," Dr. Ship said.
"Long-term salivary hypofunction
causes new and recurring dental
caries; fungal infections; difficulties
in chewing, tasting, and swallowing;
and impaired retention of
dentures, and further, oral-facial
pain, nutritional compromise, and
impaired communication impair
quality of life for many years."
High-Density Radiotherapy Plus Amifostine
Dr. Ship described a clinical
investigation of combined high-
dose rate intraoperative radiotherapy
(HD-IORT), EBRT, and amifostine.
He has partnered with Dr.
Kenneth Hu at Beth Israel Medical
Center, New York, for this innovative
approach. The protocol included
surgery to the primary site
and the neck, with intraoperative
delivery of 12 to 15 Gy to the site of
tumor (brachytherapy), postoperative
EBRT (50 to 60 Gy), and concomitant
use of amifostine (SC 1
hour prior to RT). He said that
HD-IORT dose escalation provides
improved locoregional control,
shortens total treatment duration,
and decreases toxicity by
reducing the EBRT dose. Applicators
are made of flexible silicon
that can be tailored to fit easily into
the tumor bed.
The study hypothesis is that the
combination of HD-IORT and
EBRT with a cytoprotectant (amifostine)
will reduce radiationinduced
mucositis and xerostomia
in head and neck cancer patients.
Inclusion criteria include oral cavity
oropharynx, larynx, and hypopharynx
squamous cell carcinoma
with spread to regional
lymphatics, with surgery of both
the primary site and neck, no evidence
of distant metastases, and
no previous radiotherapy or chemotherapy.
Quality of life and performance
assessments include ECOG (Eastern
Cooperative Oncology Group)
Performance Status, RTOG (Radiation
Therapy Oncology Group)
Late Radiation Morbidity Scoring
Scheme, RTOG Pharynx and
Esophagus Toxicity Grading,
FACT (Functional Assessment of
Cancer Therapy) Head and Neck,
the Terrell Head and Neck Quality
of Life Instrument, and the List
Performance Status Survey.
Salivary function and xerostomia
are assessed using the Xerostomia
Score, Xerostomia Questionnaire,
Xerostomia Quality of
Life Questionnaire, and salivary
collection (both unstimulated and
stimulated whole saliva). Mucositis
and pharyngitis assessment include
the WHO (World Health
Organization) Mucositis Grade,
CTC (Common Toxicology Criteria)
v. 2 Mucositis Grade, CTC v. 2
Pharyngitis Grade, CTC v. 2 Dermatitis
Grade, and CTC v. 2 Dysphagia
Two Patients Enrolled
Dr. Ship said that so far, the
study includes one 50-year-old
male enrolled with 9-month post-
RT data and one 61-year-old male
who just completed RT. The 50-
year-old patient who has completed
RT had a moderately differentiated
squamous cell carcinoma of
the right neck (stage IV, N2b M0).
He underwent surgical removal of
the tumor with unilateral neck dissection
and was then treated with
12 Gy of HD-IORT, 50 Gy of EBRT,
and 500 mg SC amifostine daily.
"There were no significant adverse
events and no treatment interruptions,"
Dr. Ship said.
The 50-year-old patient who has
completed treatment had mild mucositis
with erythema of the mucosa
during the second to sixth
week of EBRT. "The score returned
to baseline (grade 0) at all
post-EBRT visits," Dr. Ship reported.
Similarly, mucositis, pharyngitis,
and dysphagia were grade 0 or
1 during EBRT and all returned to
grade 0 at 1 month post-EBRT.
Fatigue and radiation dermatitis
were grade 0 or 1 during RT and
returned to grade 0 at 1 month
Better Salivary Function, QOL
"At the completion of EBRT
there was an approximately 80%
decrease in both unstimulated and
stimulated whole salivary flow
rates. There was persistent salivary
hypofunction at 9 months post-
EBRT, with slight recovery of stimulated
flow rates to 65% of pretreatment
function. The patient
had persistent xerstomia (RTOG
Late Radiation Morbidity, grade
2), from treatment until 6 months
post-EBRT; it improved to grade 1
at 9 months post-EBRT. The Xerostomia
Score decreased to 1 at 9
months post-EBRT," Dr. Ship said.
Quality of life scores were striking.
The patient had "nearly perfect"
scores at 1, 3, 6, and 9 months
post-EBRT for Head and Neck
QOL Scale, FACT Head and Neck
Scale, List Performance Status
Survey, and Xerostomia Quality
of Life Scale.
"HD-IORT and amifostine were
well tolerated and may reduce
treatment-induced oral mucositis.
This combination therapeutic approach
did not produce short-term
salivary preservation, but there
were few xerostomia-related quality-
of-life problems," Dr. Ship said.
"Despite the dramatic losses in
whole unstimulated and stimulated
saliva up to 9 months post-RT,
complaints of xerostomia were few,
and xerostomia-related quality-oflife
problems were minimal. This
may be due to preservation of
mucosal tissues during treatment,"
Dr. Ship cautioned that these results
are very preliminary and based
on a very small sample size but are
worthy of further research.