Abstract

Introduction: Head and neck squamous cell carcinomas (SCCs) constitute 5.4% of all cancers worldwide, and 23% of all cancers in males and 6% of all cancers in females diagnosed in India. Lots of ambiguity exists in primary, nodal, and metastatic workup of these patients, especially in developing countries. Aim: The study was designed to compare the accuracy of whole-body positron emission tomography/computed tomography (WBPET/CT) scan with contrast-enhanced CT (CECT) face and neck as pretreatment evaluation for staging workup and management decision and to confirm the nodal findings on imaging with fine-needle aspiration cytology (FNAC). Design: It was a single-institute, prospective, observational, interventional study over a 2-year period. All cases of SCC of upper aerodigestive tract who were scheduled for definitive treatment concurrent chemoradiotherapy or radiotherapy were evaluated with routine investigations followed by imaging in the form of CECT face and neck and 18F-fluorodeoxyglucose (FDG) WBPET/CT. Results: In the 40 enrolled patients, all underwent CECT face and neck and WBPET/CT. During initial workup, biopsy was taken from primary site and FNAC was done from neck nodes for diagnosis and for staging. In 40 patients, CECT neck showed nodal metastasis in 39 patients; however, FNAC came positive in 38 cases. PET/CT showed nodal metastasis in 38 patients; however, FNAC came positive in 38 cases. Any node with Standardized uptake value (SUV) >2.5 was taken as suspicious lesion and FNAC was done. Sensitivity of CECT and PET/CT was 97.36% and 100%, respectively, while the specificity was 0% and 100%, respectively. Positive predictive value calculated for CECT and WBPET was 94.87% and 100%, respectively, while the negative predictive value for CECT and WBPET was 0% and 100%, respectively. Conclusion: In head and neck SCC, FDG-PET/CT is more accurate than CECT in staging of the neck.

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>

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>

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.

| Figure 1  Pretreatment comparison in contrast-enhanced computed tomography and positron emission tomography/computed tomography in detecting T-stage

| 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].

1.  Ries LA, Melbert D, Krapcho M, Stinchcomb DG. editors SEER Cancer Statistics Review 1975-2005. Bethesda MD:
2.  National Cancer Registry Programme. Biennial Report (1988-1989) of the National Cancer Registry Programme. New Delhi: Indian Council of Medical Research, Surya Printers; 1992: 3-42
3.  Hermans Robert. Head and Neck Imaging Technique. P31-42,49-56
4.  Seminar in surgical Oncology. National cancer Institute, TMH 1989;5305-309
5.  Bourhis J, Le Maître A, Baujat B, Audry H, Pignon JP. Meta-Analysis of Chemotherapy in Head, Neck Cancer Collaborative Group. et al. Individual patients' data meta-analyses in head and neck cancer. Curr Opin Oncol 2007; 19: 188-94
6.  Gordin A, Daitzchman M, Doweck I, Yefremov N, Golz A, Keidar Z. et al. Fluorodeoxyglucose-positron emission tomography/computed tomography imaging in patients with carcinoma of the larynx: Diagnostic accuracy and impact on clinical management. Laryngoscope 2006; 116: 273-8
7.  Scarfone C, Lavely WC, Cmelak AJ, Delbeke D, Martin WH, Billheimer D. et al. Prospective feasibility trial of radiotherapy target definition for head and neck cancer using 3-dimensional PET and CT imaging. J Nucl Med 2004; 45: 543-52
8.  Sullivan BP, Parks KA, Dean NR, Rosenthal EL, Carroll WR, Magnuson JS. et al. Utility of CT surveillance for primary site recurrence of squamous cell carcinoma of the head and neck. Head Neck 2011; 33: 1547-50
9.  Hannah A, Scott AM, Tochon-Danguy H, Chan JG, Akhurst T, Berlangieri S. et al. Evaluation of 18 F-fluorodeoxyglucose positron emission tomography and computed tomography with histopathologic correlation in the initial staging of head and neck cancer. Ann Surg 2002; 236: 208-17
10.  Schmid DT, Stoeckli SJ, Bandhauer F, Huguenin P, Schmid S, von Schulthess GK, Goerres GW. et al. Impact of positron emission tomography on the initial staging and therapy in locoregional advanced squamous cell carcinoma of the head and neck. Laryngoscope. 2003; 113: 888-9150
11.  Ng SH, Yen TC, Liao CT, Chang JT, Chan SC, Ko SF. et al. 18F-FDG PET and CT/MRI in oral cavity squamous cell carcinoma: A prospective study of 124 patients with histologic correlation. J Nucl Med 2005; 46: 1136-43.

| Figure 1  Pretreatment comparison in contrast-enhanced computed tomography and positron emission tomography/computed tomography in detecting T-stage

| 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

1.  Ries LA, Melbert D, Krapcho M, Stinchcomb DG. editors SEER Cancer Statistics Review 1975-2005. Bethesda MD:
2.  National Cancer Registry Programme. Biennial Report (1988-1989) of the National Cancer Registry Programme. New Delhi: Indian Council of Medical Research, Surya Printers; 1992: 3-42
3.  Hermans Robert. Head and Neck Imaging Technique. P31-42,49-56
4.  Seminar in surgical Oncology. National cancer Institute, TMH 1989;5305-309
5.  Bourhis J, Le Maître A, Baujat B, Audry H, Pignon JP. Meta-Analysis of Chemotherapy in Head, Neck Cancer Collaborative Group. et al. Individual patients' data meta-analyses in head and neck cancer. Curr Opin Oncol 2007; 19: 188-94
6.  Gordin A, Daitzchman M, Doweck I, Yefremov N, Golz A, Keidar Z. et al. Fluorodeoxyglucose-positron emission tomography/computed tomography imaging in patients with carcinoma of the larynx: Diagnostic accuracy and impact on clinical management. Laryngoscope 2006; 116: 273-8
7.  Scarfone C, Lavely WC, Cmelak AJ, Delbeke D, Martin WH, Billheimer D. et al. Prospective feasibility trial of radiotherapy target definition for head and neck cancer using 3-dimensional PET and CT imaging. J Nucl Med 2004; 45: 543-52
8.  Sullivan BP, Parks KA, Dean NR, Rosenthal EL, Carroll WR, Magnuson JS. et al. Utility of CT surveillance for primary site recurrence of squamous cell carcinoma of the head and neck. Head Neck 2011; 33: 1547-50
9.  Hannah A, Scott AM, Tochon-Danguy H, Chan JG, Akhurst T, Berlangieri S. et al. Evaluation of 18 F-fluorodeoxyglucose positron emission tomography and computed tomography with histopathologic correlation in the initial staging of head and neck cancer. Ann Surg 2002; 236: 208-17
10.  Schmid DT, Stoeckli SJ, Bandhauer F, Huguenin P, Schmid S, von Schulthess GK, Goerres GW. et al. Impact of positron emission tomography on the initial staging and therapy in locoregional advanced squamous cell carcinoma of the head and neck. Laryngoscope. 2003; 113: 888-9150
11.  Ng SH, Yen TC, Liao CT, Chang JT, Chan SC, Ko SF. et al. 18F-FDG PET and CT/MRI in oral cavity squamous cell carcinoma: A prospective study of 124 patients with histologic correlation. J Nucl Med 2005; 46: 1136-43