Keywords Computed tomography scan - fine-needle aspiration cytology - Head and Neck Cancers
- positron emission tomography scan
Introduction
Extracranial head and neck carcinomas constitute 5.4% of all cancers worldwide,[1 ] and 23% of all cancers in males and 6% of all cancers in females diagnosed in India.[2 ] Most head and neck cancers are squamous cell carcinomas (SCCs) of the oral cavity,
oropharynx, larynx, or nasopharynx. The head and neck region is a region of considerable
anatomical and functional complexity, making the accurate staging of head and neck
neoplasm a challenging task. Imaging constitutes a vital component of the primary
and metastatic workup of these lesions. The current radiological modalities provide
a reliable visualization of head and neck structure to an unprecedented level of detail.
Imaging techniques such as multidetector computed tomography (CT), magnetic resonance
imaging (MRI), positron emission tomography (PET)-CT are now available and allow detailed
morphological display of the extent of disease in head and neck region.
PET has been utilized since the 1970s for clinical imaging. PET scanning with 18-fluorodeoxyglucose
(18-FDG) can be used for staging and evaluation of recurrence for primary head and
neck tumors. The principle for PET is based on the metabolism of the neoplasm, primary
or recurrent, and is more sensitive than CT or MRI for T1-staged lesions.[3 ] The most recent innovation in PET systems is the hybrid PET/CT scanners. Integration
of PET with CT scan in 2000 was a great leap forward and enhanced the clinical information
from PET.
The purpose of this study was to evaluate the PET-CT and CT scan of the head and neck
region in the primary staging of patients with cancers of the head and neck region
and to establish a protocol comprising the choice of the initial diagnostic modality
to be used in the imaging of head and neck cancer at our tertiary care government
center.
Materials and Methods
It was a prospective, observational study conducted in the radiotherapy department
of a tertiary care multispecialty government hospital. The study included 40 consecutive
patients with carcinoma of the head and neck region presenting in the department of
ENT and oncology center. All the patients were subjected to a detailed clinical examination
and endoscopic evaluation of the extent of the disease. Fine-needle aspiration or
biopsy of the lesion and lymph node was accepted for histopathological confirmation.
All the patients were evaluated with CT and PET/CT scan, and the findings were correlated
with clinical findings. The patients were treated with concurrent chemoradiotherapy
or radiotherapy as per the standard of care. This study was completed over a period
of 22 months from April 1, 2014, to February 28, 2016.
The inclusion criteria were clinical suspicion of malignancy in the oral cavity, oropharyngeal,
or laryngopharyngeal region; histopathological confirmation by biopsy; Karnofsky Performance
Score (KPS) ≥70% at time of screening; life expectancy of >6 months; no major comorbid
medical conditions; and hemogram and biochemical parameters within normal limits.
The major exclusion criteria were patients under 18 years of age, pregnant or lactating
females, failure to obtain informed consent, patients with dual malignancy, patients
already treated cases of head and neck malignancy, patients with KPS <60%, and patients
with major medical comorbidities.
The study was conducted in the department of radiation oncology in collaboration with
the department of nuclear medicine and department of radiodiagnosis. After detailed
history and general physical examination, the patients underwent baseline CT and PET
scan. All CT and PET scan images were analyzed a by a radiologist and a nuclear medicine
physician. Any area of focal greater than background muscle uptake was considered
pathological (malignant lesion) and correlated with signs, symptoms, and clinical
examination findings. Positive PET scan and CT scan findings were correlated with
clinical findings and histopathological findings. Any discordant findings were investigated
by subjecting the positive lesion to biopsy and histopathological examination after
clinical examination. In case of positive findings, histopathology of the same lesion
was taken as gold standard in describing it malignant or nonmalignant.
The patients were treated with concurrent chemotherapy with radiotherapy. The radiation
therapy was delivered at this institute. Patients treated with a total dose of 70
Gy/35# (2 Gy/5 #/week), with weekly concurrent chemo-injection cisplatin. The study
was carried out after taking written consent from all patients and clearance from
ethical committee.
Results
The analysis of data was done using SPSS software version 15.0 (Chicago, IL). Chi-square
test and Fisher's exact test were applied to find the association between two qualitative
variables. The inferences were drawn at 5% level of significance, and hence, P < 0.05 was considered statistically significant. Sensitivity, specificity, positive
predictive value, negative predictive value (NPV), and diagnostic accuracy with its
statistical significance were also calculated to see the agreement with histopathology
(biopsy/fine-needle aspiration cytology [FNAC]).
In our study, male to female ratio is 9:1. The most common decade of presentation
was 50–60 years. The youngest patient was 28 years old while the Eldest was 74 years
old; mean age was 57, while the age distribution is as shown in [Table 1 ]. Smokers: nonsmoker ratio was 9:1. Most common histology was SCC seen in 39 out
of 40 cases. The Commonest site was oropharynx as seen in 45% of cases [Table 2 ] and the most common subsite was base of tongue [Table 3 ]. The most common stage of presentation was Stage IV as seen in 62.5% of cases.
Table 1
Age distribution of cases
Age interval
Frequency (%)
SD - Standard deviation
≤30
1 (2.5)
30-40
1 (2.5)
40-50
6 (15)
50-60
20 (50)
60-70
10 (25)
>70
2 (5)
Total
40 (100)
Mean
57.4
SD
9.057650117
Table 2
Site of primary tumor in patients
Disease
Frequency (%)
Nasopharynx
1 (2.5)
Larynx
7 (17.5)
Oropharynx
18 (45)
Hypopharynx
11 (27.5)
Oral cavity
3 (7.5)
Total
40 (100)
Table 3
Subsite of tumor in patients
Tumor
Number of cases (n =40)
Site
Subsite
Nasopharynx
1
Larynx
Epiglottis
4
Aryepiglottic folds
3
Arytenoids
0
False cord
0
Ventricle
0
Glottis
0
Subglottis
0
Oropharynx
Base of tongue
12
Tonsil
6
Soft palate
0
Uvula
0
Pharyngeal wall
0
Hypopharynx
Pyriform sinus
10
Postcricod region
1
Posterior pharyngeal wall
0
Oral cavity
Lip
0
Buccal mucosa
0
Lower alveolus
0
Retromolar trigone
1
Anterior 2/3rd of tongue
2
Floor of mouth
0
Alveolar ridge
0
Hard palate
0
CECT scan of the face and neck and whole-body PET-CT scan were done in all patients
before treatment. There was no difference in detecting primary site of tumor, and
T-staging in both CECT and PET/CT groups detected the same result [Table 4 ] and [Figure 1 ]. In detecting N-stage of tumor in the study cases, diagnostic accuracy of CECT was
92.5% and of PET-CT was 100% [Table 5 ] and [Figure 2 ].
Table 4
Pretreatment comparison of T-stage by contrast-enhanced computed tomography and positron
emission tomography-computed tomography (no discrepancy noted)
T-stage
Frequency (%)
CECT
PET
Final
CECT - Contrast-enhanced computed tomography; PET - Positron emission tomography
T1
1 (2.5)
1 (2.5)
1 (2.5)
T2
23 (57.5)
23 (57.5)
23 (57.5)
T3
6 (15)
6 (15)
6 (15)
T4
10 (25)
10 (25)
10 (25)
Total
40 (100)
40 (100)
40 (100)
Figure 1: Pretreatment comparison in contrast-enhanced computed tomography and positron
emission tomography/computed tomography in detecting T-stage
Table 5
Diagnostic accuracy of contrast-enhanced computed tomography in detecting N-stage
of tumor (92.5% for contrast-enhanced computed tomography and 100% for positron emission
tomography-computed tomography)
N-stage
Frequency (%)
CECT
PET
Final (HPR)
CECT - Contrast-enhanced computed tomography; PET - Positron emission tomography;
HPR - Histopathological response
N0
1 (2.5)
2 (5)
2 (5)
N1
16 (40)
16 (40)
16 (40)
N2
20 (50)
19 (47.5)
19 (47.5)
N3
3 (7.5)
3 (7.5)
3 (7.5)
Total
40 (100)
40 (100)
40 (100)
Figure 2: Pretreatment comparison in contrast-enhanced computed tomography and positron
emission tomography/computed tomography in detecting N-stage according to tumor/node/metastasis
staging
During initial workup, biopsy was taken from primary site and FNAC was done from neck
nodes for diagnosis and for staging. The results of CECT and PET-CT for detecting
nodal status before treatment are tabulated in [Table 6 ] and [7 ], respectively. In 40 patients, CECT neck showed nodal metastasis in 39 patients;
however, FNAC came positive in 38 cases. Sensitivity of CECT for detecting nodal status
was 97.37%, specificity was 0%, predictive value of positive test was 94.87%, predictive
value of negative test was 0, and diagnostic accuracy was 92.5%; P value (Fisher's exact test) being 1.000. In 40 patients, PET-CT neck showed nodal
metastasis in 38 patients, and the FNAC came positive in all 38 cases. Sensitivity
of PET/CT for detecting nodal status was 100%, specificity was 100%, predictive value
of positive test was 100%, predictive value of negative test was 100%, and diagnostic
accuracy is 100%; P value (Fisher's exact test) being 0.001 [Table 7 ].
Table 6
Result of contrast-enhanced computed tomography for detecting nodal status before
treatment
CECT
HPR
Total
Positive
Negative
P (Fisher’s exact test) =1.000. CECT - Contrast-enhanced computed tomography; HPR -
Histopathological response
Positive
37
2
39
Negative
1
0
1
Total
38
2
40
Sensitivity
97.36842105
Specificity
0
Predictive value of positive test
94.87179487
Predictive value of negative test
0
Percentage of false negative
2.631578947
Percentage of false positive
100
Diagnostic accuracy
92.5
Table 7
Result of positron emission tomography-computed tomography scan for detecting nodal
status before treatment
PET
HPR
Total
Positive
Negative
P (Fisher’s exact test) =0.001. In 40 patients, PET CT showed nodal metastasis in 38
patients; however, FNAC came positive in 38 cases. HPR - Histopathological response;
PET - Positron emission tomography; FNAC - Fine needle aspiration cytology; PET-CT
- Positron emission tomography-computed tomography
Positive
38
0
38
Negative
0
2
2
Total
38
2
40
Sensitivity
100
Specificity
100
Predictive value of positive test
100
Predictive value of negative test
100
Percentage of false negative
0
Percentage of false positive
0
Diagnostic accuracy
100
Discussion
Cancer of the oral cavity comprises approximately 30% of head and neck region tumors
and 3% of all cancers in the United States. Head and neck cancers are common in India
and account for about 30% of cancers in males and about 13% in females. In males,
oral cavity and pharynx are the commonly affected sites, followed by larynx. In females,
oral cavity is the preponderant site.[4 ] Despite advances in the treatment of head and neck cancer, 15%–50% of the patients
will develop recurrent disease.[5 ]
For initial workup routine investigations, chest X-ray, CECT, or MRI face and neck
are recommended. PET scan is recommended only in advanced cases (Stage III and IV).
In our study, initial CECT and PET/CT both detected primary tumor in all patients
(sensitivity 100%). This does not match with sensitivities and specificities quoted
in the literature,[6 ]
[7 ]
[8 ] which quotes better sensitivity of PET/CT than CT alone. Lower sensitivity of CECT
is related to the fact that early of submucosal lesion may be difficult to detect
and differentiate from adjacent soft tissue on anatomical imaging. However, in our
study, all cases were Stage III and beyond only one Stage II case. According to tumor/node/metastasis
staging, T1 – 2.5%, T2 – 57.5%, T3 – 15%, and T4 – 25%. Same sensitivity of PET/CT
and CECT in our study could be attributed to late presentation.
According to the study done by Hannah et al .,[9 ] sensitivity and specificity for the presence of metastatic neck disease on FDG-PET
were 82% and 100%, respectively; those for CT were 81% and 81%, respectively, in our
study. The sensitivity and specificity for the presence of metastatic neck disease
on FDG-PET were 100% and 100%, those for CT 97.36% sensitive, accuracy of CECT was
92.5%. FDG-PET was true positive for metastatic neck disease in two of the three CT
false-negative patients.
According to a study done by Schmid et al ., for evaluating metastatic disease in the cervical lymph nodes, PET-CT was superior
to conventional imaging. An average sensitivity of 87%–90% and a specificity of 80%–93%
were reported for PET/CT, compared with a sensitivity of 61%–97% for CECT/MRI.[10 ]
The accuracy of 18F-FDG-PET, CT/MRI, and their visual correlation for the identification
of primary tumors was 98.4%, 87.1%, and 99.2%, respectively. The sensitivity of 18F-FDG-PET
for the identification of nodal metastases on a level-by-level basis was 22.1% higher
than that of CT/MRI (74.7% vs. 52.6%, P < 0.001), whereas the specificity of 18F-FDG-PET was 1.5% lower than that of CT/MRI
(93.0% vs. 94.5%, P = 0.345). The sensitivity and specificity of the visual correlation of 18F-FDG-PET
and CT/MRI were 3.2% and 1.5% higher than those of 18F-FDG-PET alone (77.9% vs. 74.7%,
P = 0.25; 94.5% vs. 93.0%, P = 0.18; respectively). The area under the curve obtained from the receiver operating
characteristic curve showed that 18F-FDG-PET was significantly superior to CT/MRI
for total nodal detection (0.896 vs. 0.801, P = 0.002), whereas the visual correlation of 18F-FDG-PET and CT/MRI was modestly superior
to 18F-FDG-PET alone (0.913 vs. 0.896, P = 0.28).[11 ]
Conclusion
The purpose of this study was to evaluate the PET/CT scan and CT scan of the head
and neck region in the primary staging and posttreatment assessment of patients with
cancers of the head and neck region. We infer that FDG-PET/CT yields significantly
better results compared to CECT, in detecting nodal metastasis in primary staging
and in detecting residual or recurrent disease in patients with head and neck cancer.
Its high NPV can help in avoiding unnecessary invasive procedure/surgery. For locoregional
mapping of disease, PET/CT and CECT are comparable in their sensitivity for detecting
the primary lesion; however, PET/CT is more sensitive and specific than CECT in detecting
nodal metastasis in patients with head and neck. In summary, in this prospective study,
FDG-PET/CT was not found superior to CECT for initial T-staging of head and neck malignancies,
but for initial N-staging, FDG-PET/CT was superior to CECT.
Drawbacks of the study
Small sample size – Our study has 40 patients only. It is a small group. They all
were Stage III, and beyond, only one patient was diagnosed as Stage II. Although this
study was done in a government setup where the patients did not have to pay for PET/CT,
in private sector, cost of one PET scan is approximately INR 20,000 and cost of one
CECT is INR 3000–5000, which can escalate the cost of management and burn a hole in
patient's pocket. Moreover, there was room for observer variation. Being a government
hospital, every time reports were given by different radiologists and nuclear medicine
specialists and they were reviewed by different head and neck oncologist. Larger prospective
studies are warranted to stabiles the definitive role in the management protocols
and cost-effectiveness of FDG-PET/CT in the management of head and neck cancers.
