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ORAL CAVITY MASS
Rivera, Laila Marie C.
Rivere, Djeaune Marie Trissel B.
Robosa, Dean Antonio R.
Rodas, Francis Martin F.
Rodriguez, Shereen Reine S.
Rogelio, Ma.Graciela A.
Roque, Marianne N.
Ruanto, Maria Theresa R.
38 Y/O M
6 mos PTC
2 mos PTC
1 mo PTC
•2x2cm ulcer in the left lower gingiva
•firm mass in the left submandibular area
•mass at left lateral neck at the level of the
lower third of the SCM
•admitted because of oral ulcer
Review of System
• negative
Past Medical History
• Negative
Personal/Social History
• 10 pack year smoking history
• (+) alcoholic beverage drinker
Physical Examination
• Oral cavity: 2x2 cm ulcer, lower gingiva near the
retromolar trigone
• Neck: 4x4 cm firm, well-delineated, slightly movable
mass at the left jugulo-digastric area; 3x3 cm firm, welldelineated, movable mass at the lower third of the SCM
• Thyroid gland: negative for masses
SALIENT FEATURES







Oral cavity: 2x2 cm
ulcer, lower gingiva
near the retromolar
trigone
 Neck: 4x4 cm firm, welldelineated, slightly
movable mass (left
jugulo-digastric area);
2x2cm ulcer (left lower
3x3 cm firm, wellgingiva)
delineated, movable
firm mass (left
mass (lower third of the
submandibular area)
SCM)
mass (left lateral neck;
level of the lower third of  Thyroid gland: (-)
masses
the SCM)
38 y/o
M
10 pack year smoking
history
(+) alcoholic beverage
drinker

1. WHAT IS YOUR CLINICAL
IMPRESSION?
DIFFERENTIAL DIAGNOSIS
TB adenopathy
Lymphoma
Lymphadenitis
from aphthous
ulcer
Metastatic
carcinoma from
oral cavity
cancer
TB ADENOPATHY
… in developing countries…
 Tuberculosis: most common cause of cervical lymph
node enlargement
 Peripheral lymph node tuberculosis is the most
common form of extrapulmonary tuberculosis
 Cervical tuberculous lymphadenopathy (scrofula) is still
the most common cause of persistent cervical lymph
node enlargement



unilateral, with little or no pain, advanced disease may
suppurate and form a draining sinus
diagnosis is established by fine-needle aspiration or
surgical biopsy



AFB are seen in up to 50% of cases
cultures are positive in 70 to 80%
histologic examination shows granulomatous lesions
http://pmj.bmj.com/cgi/content/full/77/905/185#SEC3
http://www.javeriana.edu.co/Facultades/Medicina/pediatria/revis/
eMedicine%20-%20Tuberculosis%20%20Article%20by%20Thomas%20Herchline,%20MD.htm
LYMPHOMA
Lymphoma may be nodal or extranodal
 A quarter of all extranodal lymphomas occur in the
head and neck


Extranodal lymphoma is usually NHL
8% of findings on supraclavicular fine-needle aspirate
biopsy yield a diagnosis of lymphoma
 Lymphoma is the second most common primary
malignancy occurring in the head and neck
 Incidence of aggressive non-Hodgkin lymphoma has
risen steadily over recent decades

http://emedicine.medscape.com/article/854110-overview
NON-HODGKIN’S LYMPHOMA
 May
manifest in the cervical region and
lymphoid tissue of the Waldeyer ring
 Appears as a mass in the oropharynx or
nasopharynx
 Unilateral tonsillar enlargement is highly
suggestive of malignancy.
 Usually arises in the tongue base
 In contrast to squamous cell carcinoma, NHL is
bulky, fleshy, and nonulcerating
 Some patients with indolent NHLs may have
large asymptomatic abdominal masses

Splenic or hepatic enlargement
http://emedicine.medscape.com/article/854110-overview
LYMPHADENITIS FROM APHTHOUS
ULCER
 lymphadenitis
is an infection of the lymph
nodes; a complication of bacterial infection
 swollen glands are usually found near the
site of an underlying infection, tumor, or
inflammation  apthous ulcer



Apthous ulcer also known as APHTHOUS
STOMATITIS
painful open sore inside the mouth, caused by
a break in the mucous membrane
Etiology is unknown
 Lymphadenitis
may occur after skin
infections or other bacterial infections,
particularly those due to streptococcus or
staphylococcus
METASTATIC CARCINOMA FROM ORAL
CAVITY CANCER
 5%

percent of all cancers reported yearly
30% of these cancers occur in the oral cavity
 squamous
cell carcinoma- (most common) 95% of
oral cavity cancer
 Risk Factors:

use of tobacco/ smoking
80% of patients with oral SCC
 risk of developing malignancy is 5-9 times greater for
smokers than nonsmokers




Alcohol- 3-9 times greater risk of developing cancer
of alcohol and tobacco combined may convey a risk
greater than 100 times the general population
HPV types 16 and 18 may be found in
approximately 22% and 14% of oropharyngeal
tumors
http://www.ahns.info/patienteducation/docs/oralcavity.php
http://emedicine.medscape.com/article/847678-overview
METASTATIC CARCINOMA FROM
ORAL CAVITY CANCER
Symptoms
 most common presentation of cancer of the
floor of the mouth is a painless inflamed
superficial ulcer with poorly defined margin
 Intermittent bleeding may occur
 Advanced cases: complaints may include new
or increased pain, pain on swallowing, ear
pain, a change in speech, uncoordinated
swallowing, or a lump in the neck


sores in the mouth, whether they are related to
trauma or to a variation of canker (apthous)
sores, should fully heal within three weeks
http://www.ahns.info/patienteducation/docs/oralcavity.php
METASTATIC CARCINOMA FROM
ORAL CAVITY CANCER
Metastatic neck disease is the most important
factor in the spread of head and neck squamous
cell carcinoma (SCC) from primary sites
 most commonly involved primary sites



larynx, oropharynx, hypopharynx, and oral cavity
Malignant tumors of the oral cavity grow rapidly,
with frequent and early metastasis to the
surrounding regional lymph nodes
http://emedicine.medscape.com/article/850195-overview
CLINICAL IMPRESSION:
METASTATIC CARCINOMA FROM
ORAL CAVITY CANCER
2. WHAT TO DO NEXT
WHAT TO DO NEXT



Perform a thorough head and neck exam under
anesthesia
Perform triple endoscopy:
(nasopharyngolaryngoscopy, bronchoscopy,
esophagoscopy)
Get a biopsy of the oral cavity ulcer
THOROUGH HEAD AND NECK EXAM
Biopsy of primary
 Fine needle aspiration of possible neck
metastasis
 Imaging studies:

Chest radiograph: posteroanterior and lateral
 CT/MRI of primary and neck
 Panorex or dental x-ray: evaluate mandible invasion
if CT/MRI not performed
 Barium swallow

THOROUGH HEAD AND NECK EXAM

Laboratory tests
Pre anesthesia testing
 Basic liver function tests

Consutations:
-Radiation therapy -for adjuvant or definitive therapy
considerations
-Dental: pre radiation dental treatment and for post
therapy
EXAMINATION UNDER ANESTHESIA
Nasopharyngolaryngoscopy and pharyngoscopy
 Esophagoscopy
 Bronchoscopy

NASOPHARYNGOLARYNGOSCOPY

diagnostic medical
procedure that uses a
flexible fibreoptic endoscope to
visualize the
structures inside the
nasal passages,
including
the sinus openings,
the larynx, and
the vocal cords.
PHARYNGOSCOPY

technique of placing a
rigid or flexible
endoscope via the mouth
to visualise the pharynx
(back of the throat).
This technique provides
direct visualisation of
this structure under
magnification allowing
structural abnormalities
to be diagnosed and any
diseased areas to be
accurately sampled
(biopsied).
ESOPHAGOSCOPY

direct visual
examination of the
esophagus with an
esophagoscope.
Esophagoscopy
usually is done as a
diagnostic procedure
for the purpose of
locating and
inspecting a disorder
of the esophagus
BRONCHOSCOPY

Bronchoscopy is
a technique of
visualizing the inside of
the airways for
diagnostic and
therapeutic purposes.
An instrument
(bronchoscope) is
inserted into the
airways, usually
through the nose or
mouth, or occasionally
through a tracheostomy
FINDINGS:


Nasopharyngolaryngoscopy ⊖; Biopsy of ulcer: welldifferentiated squamous cell cancer
Fine needle biopsy of neck mass: Chronic
Lymphadenitis
3. WHAT WILL YOU DO NEXT?
OVERVIEW OF MANAGEMENT
Metastatic
Work-up
Staging
Imaging for
Resectability
Surgery
Radiotherapy
LYMPH NODE BIOPSY
 The
goal of lymphatic mapping and sentinel
lymph node biopsy is to identify and remove
the lymph node most likely to contain
metastases in the least invasive fashion.
*
Sentinel node - the first node to receive drainage from
the tumor site. This node is the node most likely to
contain metastases, if metastases to that regional lymph
node basin are present.
 Recent
studies evaluating treatment of an
N0 neck have investigated the use of
sentinel lymph node biopsy, which attempts
to predict the disease status of the neck
based on the first echelon of nodes that
drain the tumor.
METASTATIC WORK-UP
 Vigilance
for second primary tumors
 Patients
diagnosed with a head and neck
cancer are predisposed to the development
of a second tumor within the aerodigestive
tract
 Patients
with a primary malignancy of the
oral cavity or pharynx are most likely to
develop a second lesion within the cervical
esophagus

Once cancer has been proven by biopsy, a CT scan of the chest
will be ordered to rule out distant metastasis
Contrast-enhanced CT and MRI of the head and neck may be
performed for evaluation of the tumor and detection of occult
lymphadenopathy

CT scanning - best at evaluating bony destruction

MRI - determine soft tissue involvement and is excellent at
evaluating parotid and parapharyngeal space tumors

Chest radiography or chest CT is performed to rule out
synchronous lung lesions

Serum tumor markers such as alkaline phosphatase and
calcium may be determined, but such tests are not standard.

Positron Emission Tomography (PET)




evaluates neck metastases with a sensitivity equal to
that of CT
able to detect a higher percentage of lung metastases
than chest radiography, bronchoscopy, or CT
but specificity ranges from 50% to 80%, and how to
treat a patient with a positive PET and an otherwise
negative lung workup is still in question
most common sites of distant spread are the lungs
and bones, whereas hepatic and brain metastases
occur less frequently
risk for distant metastases is more dependent on
nodal staging than on primary tumor size
STAGING

Clinical staging of the neck is based primarily on
palpation, although radiographic studies,
including computed tomography (CT) and
magnetic resonance imaging (MRI), have been
shown to be accurate in detecting positive nodes
T1N2bMX
IMAGING FOR RESECTABILITY
Panoramic x-ray of the mandible
 scanning dental X-ray of the upper and lower jaw
 shows a two-dimensional view of a half-circle
from ear to ear
 shows a patient's nasal area, sinuses, jaw joints,
teeth and surrounding bone
 can reveal cysts, tumors, bone irregularities
 the mandible can also have an indentation on its
lower border when the patient's masseter has
been clenching and grinding
 shows the entire mandible, including all of its
lower border
 Indications
for cortical or rim
resection of the mandible as determined
by physical examination, CT scan,
orthopantomogram, and dental films
a. Tumor close to but not involving the periosteum
of mandible
b. Tumor involving only mandibular periosteum
c. Tumor adjacent to cortical bone of mandible with
no evidence of invasion beyond superficial cortex
d. Tumor adjacent to dentition with no evidence of
involvement of periodontal ligament
Indications for segmental resection of the
mandible as determined by physical examination, CT
scan, orthopantomogram, and dental films
a.
b.
c.
d.
e.
f.
Invasion of the medullary space of the mandible
Tumor fixation to the occlusal surface of the mandible in
the edentulous patient
Invasion of tumor into the mandible via the mandibular or
mental foramen
Tumor fixed to the mandible following prior radiotherapy
to the mandible, particularly if the tumor is located on the
occlusal surface
Tumor adjacent to carious dentition with involvement of
the periodontal ligament
Hypoplastic edentulous mandible with significant loss of
vertical height precluding safe performance of a rim
resection


Cortical or rim mandibulectomy – if (+)
adherence to mandibular periosteum without
bony erosion
Segmental resection – if (+) mandible invasion
RESECTION OF RETROMOLAR
TRIGONE TUMORS:
 usually
requires a marginal or segmental
mandibulectomy with a soft-tissue and/or
osseous reconstruction in order to
maximize a patient's postoperative ability
for functional speech and swallowing

Ipsilateral elective and therapeutic neck
dissection is performed because of the risk
of metastasis to the regional lymphatics
RESULTS OF THE PATIENT
Head & neck examinations: ⊖ Chest X-ray: ⊖
 Panoramic x-ray of the mandible: lytic lesion of the
body of the mandible near the angle

4. WHAT TYPE OF SURGERY IS
INDICATED?
WHAT TYPE OF SURGERY IS INDICATED?

Operative Findings:

3 x 2 cm ulcer of the lower gingiva with invasion into the mandible

5 X 4 cm well-encapsulated firm mass located at the submandibular triangle (level 1 to
level 2)

Multiple pinkish-red, firm, grossly enlarged nodes ( 1-2 cm) along the jugular chain (levels
2 to 4)
4 X 3 cm well encapsulated firm mass at the supraclavicular area
Operation done:




Wide excision of the ulcer with segmental mandibulectomy with modified radical neck
dissection, left; the defect was reconstructed using titanium plates
Final histopath:

Well differentiated squamous cell carcinoma with metastasis to 5/20 lymph nodes, the
largest measures 2 cm with extracapsular invasion; margins clear; with bony invasion
LYMPH NODE GROUPS
SURGICAL PRINCIPLES
Wide resection, tumor free margins
 Segmental mandibulectomy



3 x 2 cm ulcer of the lower gingiva with invasion into
the mandible
Modified radical neck dissection

Excision of lymph node levels (level I-V) with
preservation of the spinal accessory nerve, internal
jugular vein, and sternocleidomastoid muscle.
MODIFIED RADICAL NECK RESECTION
5 X 4 cm well-encapsulated firm mass located at the
submandibular triangle (level 1 to level 2)
 Multiple pinkish-red, firm, grossly enlarged nodes (
1-2 cm) along the jugular chain (levels 2 to 4)
 4 X 3 cm well encapsulated firm mass at the
supraclavicular area

MODIFIED RADICAL NECK DISSECTION
Indications:
 preservation of the spinal accessory nerve (SAN),
internal jugular vein (IJV), or
sternocleidomastoid muscle (SCM)
 N0 or N1
 N2, MRND is reasonable if any of the
aforementioned nonlymphatic structures can be
safely preserved.

OPERATIVE TECHNIQUE
Apron Incision
•flap design that extends from the mastoid tip to the mandibular symphysis
Exposure of the neck following subplatysmal flap elevation, superficial to the greater
auricular nerve and external jugular vein.
Modified radical neck dissection (MRND). Exposure following subplatysmal flap
elevation. The submental (IA) and submandibular contents (IB) have been dissected
away from the underlying soft tissues (arrow).
Modified radical neck dissection (MRND). Elevation of the level I contents out of the
submental and submandibular triangles, exposing the digastric and mylohyoid
muscles. The level I contents are now lying along the anterior border of the
sternocleidomastoid muscle.
Modified radical neck dissection (MRND). Identification of the spinal accessory nerve
anterior to the sternocleidomastoid muscle in the contralateral neck of the same
patient as it courses lateral to the internal jugular vein. A single nodal metastasis
was clinically evident in this neck and an extended supraomohyoid neck dissection
was performed.
OPERATIVE TECHNIQUE
Modified radical neck dissection (MRND). Identification of the spinal accessory nerve (SAN; arrow) posterior to the
sternocleidomastoid muscle (SCM) as it courses through the posterior triangle to the trapezius muscle. The SAN
invariably exits from the posterior border of the SCM above the point where the greater auricular nerve courses around
the SCM (arrowhead). The greater auricular nerve is coursing parallel and immediately superior to the external jugular
vein. Intraoperative evaluation of the right jugulodigastric region demonstrated extensive metastatic fixation to the
internal jugular vein. However, a plane of dissection was easily developed between the SAN and the nodal metastases.
Therefore, an MRND with preservation of the SAN was performed.
Modified radical neck dissection (MRND). The sternocleidomastoid muscle has been transected inferiorly and the
external jugular vein has been ligated. The omohyoid muscle is now visualized superficial to the carotid sheath (arrow).
The sternocleidomastoid muscle has been bisected to preserve the spinal accessory nerve as it courses towards the skull
base.
Modified radical neck dissection (MRND). The omohyoid muscle has been divided. The jugular vein has been divided and
ligated.
Modified radical neck dissection (MRND). The contents of the posterior triangle have been elevated in a posterior to
anterior direction, preserving the fascia overlying the scalene muscles, the brachial plexus, and the phrenic nerve. The
extensive nodal metastatic disease that was present around the carotid bifurcation (arrow) required reflection of the neck
dissection specimen superiorly prior to internal jugular vein ligation.
Completed modified radical neck dissection (MRND). The spinal accessory nerve is preserved and some protective fascia
remains over the carotid artery. The borders of the neck dissection are now clearly seen: superior border, inferior border
of the mandible; inferior border, clavicle; medial border, lateral border of the sternohyoid muscle, hyoid bone, and
contralateral anterior belly of the digastric muscle; lateral border, anterior border of the trapezius muscle.
OTHER SURGICAL PROCEDURES

Radical Neck Dissection

Removal of all ipsilateral cervical lymph nodes (level
I-V). Dissection from the inferior border of the
mandible to clavicle, posteriorly to the anterior
border of the trapezius muscle, and anteriorly to the
lateral border of the sternohyoid muscle. Depth is to
the fascia overlying the anterior scalene and levator
scapulae muscles.
INDICATIONS
Multiple positive neck nodes that are clinically
present in an untreated patient or in a patient
treated with surgery, irradiation, chemotherapy,
or a combination thereof
 One or more positive neck nodes that are
clinically present and extracapsular extension
with involvement of the spinal accessory nerve
and internal jugular vein

5. WHAT ADJUVANT
TREATMENT IS REQUIRED?
WHAT ADJUVANT TREATMENT IS
REQUIRED?

Stage Iva
combined modality
 Surgery + radiation
 Chemotx + radiation for advanced larynx or
hypopharynx lesions

RADIOTHERAPY
For Stage 3 & 4
 Radiation pre or postop
 Indicators for postoperative adjuvant radiation
therapy:


Presence of negative prognostic factors such as extracapsular
spread of tumor, perineural invasion, vascular invasion,
fixation to surrounding structures, and multiple positive nodes
Preoperative radiation or chemoradiation therapy

Given when patients have advanced neck disease that involves
the carotid artery or the deep neck musculature, in the hope
that the tumor reduces in size and becomes resectable.
50 to 70 Gy over 5 to 7 weeks
 Adverse Effect:



Acute: mucositis, skin erythema
Late: fibrosis, xerostomia, altered taste, risk of
osteoradionecrosis
CHEMOTHERAPY
No survival advantage for HNSCC compared to
surgery and/ or radiation
 Role of chemotherapy:

as a radiation sensitizer
 Palliation (symptom control) of recurrent or
unresectable disease, combined with radiation


Cisplatin, carboplatin, 5-FU
JOURNAL ON DIAGNOSIS
CYTOLOGIC AND DNA- CYTOMETRIC
EARLY DIAGNOSIS OF ORAL CANCER
Torsten W. Remmerbach, Horst Weidenbach, Natalja Pomjanski,
Kristiane Knops, Stefanie Mathes , Alexander Hemprich and
Alfred Böcking
Department of Oral, Maxillofacial and Plastic Surgery, University of Leipzig,
Leipzig,Germany
Institute of Pathology, University of Leipzig, Leipzig, Germany
Institute of Cytopathology, Heinrich Heine University, Düsseldorf, Germany
ABSTRACT
Squamous cell carcinomas of the oral cavity are among the ten
most common cancers in the world, accounting for approximately
3–5% of all malignancies.
•
•
•
The aim of this prospective study was to report on the
diagnostic accuracy of conventional oral exfoliative cytology
taken from white-spotted, ulcerated or other suspicious oral
lesions in our clinic.
In addition DNAimage cytometry as an adjuvant
diagnostic tool was studied
The hypothesis is that DNA-aneuploidy is a sensitive
and specific marker for the early identification of tumor
cells in oral brushings
Study design:
•
•
251 cytological diagnoses obtained from exfoliative
smears of 181 patients from macroscopically suspicious
lesions of the oral mucosa and from clinically
seemingly benign oral lesions which were exisiced for
establishing histological diagnoses were compared
with histological and/or clinical follow-ups of the
respective patients.
Nuclear DNA-contents were measured after Feulgen
restaining using a TV image analysis system.
PATIENTS AND METHODS:
 The
study population consisted of 251
cytological diagnoses on 1254 smears (at least
four smears were prepared from each brushing)
obtained from 181 patients



43% females, 57% males
with a mean age of 60 years (range 20–91 years)
had been referred for examination and treatment of
oral lesions to the Department of Oral-Maxillofacial
and Plastic Surgery.
RESULTS:


Sensitivity of the cytological diagnosis on oral smears for
the detectionof cancer cells was 94.6%, specificity 99.5%,
positive predictive value 98.1% and negative predictive
value 98.5%
DNA-aneuploidy was assumed if abnormal DNA-stemlines
or cells with DNA-content greater 9c were observed. On
this basis the prevalence of DNA-aneuploidy in smears of
oral squamous cell carcinomas in situ or invasive
carcinomas was 96.4%. Sensitivity of DNA-aneuploidy in
oral smears for the detection of cancer cells was 96.4%,
specificity 100%, positive predictive value 100% and
negative 99.0%

The combination of both techniques increased
the sensivity to 98.2%, specificity to 100%, positive
predictive value to 100% and negative to 99.5%.
CONCLUSIONS:
 Brush
cytology of all visible oral lesions, if they
are clinically considered as suspicious for
cancer, are an easily practicable, cheap, noninvasive, painless, safe and accurate screening
method for detection of oral precancerous
lesions, carcinoma in situ or invasive
squamous cell carcinoma in all stages.
 We conclude that DNA-image cytometry is a
very sensitive, highly specific and objective
adjuvant tool for the early identification of
neoplastic epithelial cells in oral smears.
JOURNAL ON TREATMENT
POSTOPERATIVE IRRADIATION WITH
OR WITHOUT CONCOMITANT
CHEMOTHERAPY FOR LOCALLY
ADVANCED HEAD AND NECK CANCER
Jacques Bernier, M.D., Ph.D., Christian Domenge, M.D.,
Mahmut Ozsahin, M.D., Ph.D., Katarzyna Matuszewska, M.D.,
Jean-Louis Lefebvre, M.D., Richard H. Greiner, M.D., Jordi Giralt, M.D.,
Philippe Maingon, M.D., Frederic Rolland, M.D., Michel Bolla, M.D.,
Francesco Cognetti, M.D., Jean Bourhis, M.D., Anne Kirkpatrick, M.Sc.,
and Martine van Glabbeke, Ir., M.Sc., for the European Organization for Research
and Treatment of Cancer Trial 22931
INTRODUCTION
Background
 compared concomitant cisplatin and irradiation
with radiotherapy alone as adjuvant treatment
for stage III or IV head and neck cancer.
INTRODUCTION
Objective
 to determine whether the addition of cisplatin to
high-dose radiotherapy after radical surgery
increases progression-free survival in patients at
high risk for recurrent cancer
METHODOLOGY
patient population
and eligibility criteria
Surgery
Radiotherapy
Chemotherapy
Follow-up
Patients and methods:
• After undergoing surgery with
curative intent, 167 patients
were randomly assigned to
receive radiotherapy alone (66
Gy over a period of 6 1⁄2 weeks)
and 167 to receive the same
radiotherapy regimen combined
with 100 mg of cisplatin per
square meter of body-surface
area on days 1, 22, and 43 of
the radiotherapy regimen.
METHODOLOGY
patient population
and eligibility criteria
Surgery
Radiotherapy
Chemotherapy
Follow-up
Eligibility Criteria
Patients had to have:
•
previously untreated, histologically
proven squamous-cell carcinoma arising
from the oral cavity, oropharynx,
hypopharynx, or larynx, with a tumor
(T) stage of pT3 or pT4 and any nodal
stage (N), except T3N0 of the larynx,
with negative resection margins, or a
tumor stage of 1 or 2 with a nodal stage
of 2 or 3 and no distant metastasis (M0).
•
with stage T1 or T2 and N0 or N1 who
had unfavorable pathological findings
(extranodal spread, positive resection
margins, perineural involvement, or
vascular tumor embolism)
•
with oral-cavity or oropharyngeal
tumors with involved lymph nodes at
level IV or V, according to the
anatomical lymph-node distribution
METHODOLOGY
patient population
and eligibility criteria
Surgery
Radiotherapy
Chemotherapy
Follow-up
Eligibility Criteria
Patients had to be or had to have:
• at least 18 years of age and no older than
70 years, with a performance status of 0, 1,
or 2, according to the scale of the World
Health Organization
• they also had to have a serum creatinine
concentration of 1.36 mg per deciliter (120
μmol per liter) or less
• a white-cell count of at least 4000 per cubic
millimeter
• a platelet count of at least 100,000 per
cubic millimeter
• a hemoglobin concentration of at least 11.0
g per deciliter (6.8 mmol per liter)
• Aminotransferase values and bilirubin
values could not exceed twice the upper
limit of normal were excluded from the
study.
METHODOLOGY
patient population
and eligibility criteria
Surgery
Radiotherapy
Chemotherapy
Follow-up
Exclusion Criteria
• Patients who had a history of
invasive or synchronous
cancer (except nonmelanoma
skin cancer), had previously
received chemotherapy, or
had known central nervous
system disease
METHODOLOGY
patient population
and eligibility criteria
Surgery
Radiotherapy
Chemotherapy
Follow-up
Surgery
Patients underwent primary
surgery performed with curative
intent.
The extent of surgical resection
of the primary tumor and neckdissection procedures followed
accepted criteria for adequate
excision, which depend on the
volume and location of the
tumor. If the tumor was within
5 mm of the surgical margins,
the resection margins were
considered
to be close.
METHODOLOGY
patient population
and eligibility criteria
Surgery
Radiotherapy
Chemotherapy
Follow-up
Radiotherapy
All patients received postoperative
radiotherapy consisting of
conventionally fractionated doses
of 2 Gy each in five weekly sessions
Treatments were conducted on linear
accelerators of 4 to 6 MV with the use
of isocentric techniques. A large volume
encompassing the primary site and all
draining lymph nodes at risk received a
dose of up to 54 Gy in 27 fractions over
a period of 5 1⁄2 weeks.
Regions that were at high risk for
malignant dissemination or that had
inadequate resection margins received
a 12-Gy boost (total, 66 Gy) in 33
fractions over a period of 6 1⁄2 weeks.
The dose to the spinal cord was limited to
45 Gy.
METHODOLOGY
patient population
and eligibility criteria
Surgery
Radiotherapy
Chemotherapy
Follow-up
Chemotherapy
100 mg of cisplatin per square
meter of body-surface area on
days 1, 22, and 43 of the course of
radiotherapy. Patients received
prophylactic hydration and
antiemetic agents.
METHODOLOGY
patient population
and eligibility criteria
Surgery
Radiotherapy
Chemotherapy
Follow-up
Follow-up
Patients were evaluated:
• every 2 months for the first 6 mos.
• every 4 months for the next 24
mos.
• every 6 months for the next 2 yrs
• annually thereafter.
Adverse effects, weight, performance
status,
and tumor response were assessed at
baseline,
weekly for the first eight weeks, and at
each follow up assessment.
STUDY DESIGN




Patients were randomly assigned to receive
radiotherapy alone or radiotherapy combined with
chemotherapy.
The Pocock minimization technique was used for the
randomization; center and tumor site were used as
stratification factors.
The trial was designed to detect an absolute increase
in progression-free survival of 15 percent (from 40
percent to 55 percent at three years) with a two-sided
5 percent significance level and a statistical power of
80 percent.
According to the intention-to-treat principle, no
patient was excluded from the demographic and
efficacy analysis.
STUDY DESIGN

Primary end point:
Progression-free survival = defined as the time from randomization
to any type of progression or death from any cause.
 Overall survival = defined as the time from randomization to death
from any cause.
 Both end points were estimated by means of Kaplan–Meier methods,
and comparisons between treatment groups used the log-rank test.


Second end point:




The cumulative incidences of local or regional relapses, late reactions,
metastases, and second primary tumors
Comparisons between treatment groups used Gray’s test.
All tests were two-sided. Version 2.0 of the Common Toxicity
Criteria of the Radiation Therapy Oncology Group was used to
grade adverse effects.
The Late Radiation Morbidity Scoring Scheme of the Radiation
Therapy Oncology Group and the EORTC was used to assess late
adverse effects.
CHARACTERISTICS
OF PATIENTS AND
TUMORS.
RESULTS


After a median follow-up of 60 months, the rate of
progression-free survival was significantly higher in
the combined-therapy group than in the group given
radiotherapy alone (P=0.04 by the log-rank test;
hazard ratio for disease progression, 0.75; 95 percent
confidence interval, 0.56 to 0.99), with 5-year
Kaplan–Meier estimates of progression-free survival
of 47 percent and 36 percent, respectively.
The overall survival rate was also significantly higher
in the combined-therapy group than in the
radiotherapy group (P=0.02 by the log-rank test;
hazard ratio for death, 0.70; 95 percent confidence
interval, 0.52 to 0.95), with five-year Kaplan–Meier
estimates of overall survival of 53 percent and 40
percent, respectively.
RESULTS
The cumulative incidence of local or regional
relapses was significantly lower in the combinedtherapy group (P=0.007).
 The estimated five-year cumulative incidence of
local or regional relapses (considering death from
other causes as a competing risk) was 31 percent
after radiotherapy and 18 percent after combined
therapy. Severe (grade 3 or higher) adverse
effects were more frequent after combined
therapy (41 percent) than after radiotherapy (21
percent, P=0.001)
 the types of severe mucosal adverse effects were
similar in the two groups, as was the incidence of
late adverse effects.

CONCLUSION
Postoperative concurrent administration of highdose cisplatin with radiotherapy is more
efficacious than radiotherapy alone in patients
with locally advanced head and neck cancer and
does not cause an undue number of late
complications.
References:
Schwartz’s Principles of Surgery, 8th ed.
 Sabiston Textbook of Surgery, 18th ed.
 http://www.carleconnect.com/CSP/CSP%20Fall/7.
%20Fall06.Brockenbrough.OralCancers.pdf
 http://www.lib.uiowa.edu/commons/oto/iowa/Part
3/P3G3.htm
 “Postoperative Irradiation with or without
Concomitant Chemotherapy for Locally Advanced
Head and Neck Cancer,” The new england
journal of medicine, 350;19. may 6, 2004.
Downloaded from www.nejm.org on November
15, 2009
