View of Risk Scoring System Validity for Detection of Cervical Nodal Metastasis in patients with Head and Neck Squamous Cell Carcinoma

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Annals of R.S.C.B., ISSN:1583-6258, Vol. 25, Issue 6, 2021, Pages. 12467 - 12477 Received 25 April 2021; Accepted 08 May 2021.

12467 http://annalsofrscb.ro

Risk Scoring System Validity for Detection of Cervical Nodal Metastasis in patients with Head and Neck Squamous Cell Carcinoma

Amira Abdelnaby Abdallah*⁽¹⁾, Dalia Nabil Khalifa⁽¹⁾, Mohammed Abd Alkhalak Basha⁽¹⁾, Ahmed Mohamed Alsowey⁽¹⁾

(1)Department of Radiodiagnosis, Faculty of Medicine, Zagazig University, Egypt

*Corresponding author: Amira Abdelnaby Abdallah, E-mail: [email protected]

ABSTRACT

Background: The presence of lymph node metastasis has a great impact on treatment and prognosis in patients with head and neck Squamous Cell Carcinoma. This study targeted to detect cervical node metastasis by using An accurate MDCT scoring system in patients with HNSCCC. Patients and Methods: A cross sectional study in Zagazig University Hospital during the period from November 2019 to April 2020. Included 76 lymph nodes from thirty patients with HNSCC. We analyzed preoperative CT images of lymph nodes including diameter, ratio of long to short axis diameter, necrosis and T stage of the primary tumor.

The reference standard comprised pathologic results. Multivariable logistic regression analysis was performed to evaluate the risk scoring system. Results: A risk scoring system (shortest axial diameter, L/S ratio, necrosis and T stage) showing risk of malignancy ranged from 7.3% to 99.8%, which was positively associated with increased scores. Area under curve of the risk scoring system were 0.886 with a 95%CI, 0.881-0.920.The optimism corrected performance was good (AUC=0.879, 94%CI=0.914) the hosmer-lemeshow goodness of fit test indicated the prediction model and scoring system were well calibrated (P.160).the caliberation plot showed good agreement between the predicited and actual risks of lymph node metastasis. Conclusion: A risk scoring system using CT characteristic of lymph nodes and tumors for HNSCC could be feasible to stratify the risk of cervical lymph node metastasis with high diagnostic accuracy.

Key words: Area under curve (AUC), Head and Neck Squamous cell Carcinoma (HNSCC), long-to-short (L/S),Multidetector computed tomography (MDCT).

INTRODUCTION

Cervical nodal metastases have a major influence on the prognosis of patients with squamous cell carcinoma of the head and neck region⁽¹⁾.

The appropriate diagnosis of the presence of metastatic node is very important for the management of head and neck cancer. The possibility of early detection and treatment of the head and neck cancer shows a great potential for improving the quality of life for theses cancer patients and a better prognosis ⁽²⁾.

Imaging assessment of lymph node metastasis in the head and neck can be challenging for the radiologist because there are multiple cervical levels to review and variable suggested criteria for metastatic lymph nodes. Furthermore, multiple image features of lymph nodes (including diameters, shapes and presence of necrosis), combinations of those features ,and characteristics of primary tumor (such as T-stage or location) should be considered to determine the possibility of metastasis in daily practice ⁽³⁾.

A comprehensive and systematic approach, based on a combination of previously proposed criteria, is needed to maximize the benefits of preoperative CT⁽⁴⁾.

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A simple 9 point risk scoring system using CT characteristic of lymph nodes and tumors for HNSCC to stratify the risk of cervical lymph node metastasis to facilitate individual diagnostic and therapeutic decision making⁽⁵⁾.

PATIENTS & METHODS

This study included 30 patients; they were 17 males and 13 females with their ages ranged from 25 to 81 years and their mean age of 54.32 ± 13.38 years. Our patients were referred from oncology department, Zagazig university hospitals as well as the outpatient clinic for Neck MDCT examination with intravenous contrast media during the period from November 2019 to April 2020.

Ethical approval:

Written informed consent was obtained from all participants and the study was accepted by the Research Ethics Committee of the Faculty of Medicine, Zagazig University. Study has been carried out on experiments involving human subjects in compliance with the Code of Ethics of the World Medical Association (Declaration Helsinki).

Inclusion criteria: Patients had pathologically proved HNSCC, Patients underwent a neck CT examination before the treatment of HNSCC .

Exclusion criteria: Patient has contrast media allergy,Serum creatinine level above 2mg/dl, Patient refusal to sign consent despite informed discussion, The selected patients were subjected to careful history taking ,Full clinical examination (General &

Local),Laboratory investigation (Renal function test) and MDCT imaging with intravenous contrast media and histopathological examination.

CT image acquisition: MDCT examination was performed using 128-MDCT scanner (dual source 128 slice Philips Ingenuity core). Patient was placed in supine position with arms beside the body on the bed. A scanogram was obtained with a coverage from the upper margin of the frontal sinus to the top of the aortic arch. Acquisition of CT images began 70 seconds after the injection of 140 ml of intravenous iopamidol (Isovue-370; Bracco, Princeton, New Jersey) at rate of 2.5ml/s. The scanning parameters were detector collimation 128 slices, Tube voltage 120 KV, Tube current 200 mAs, Beam collimation 0.6 mm x 128, Rotation time 0.5 sec, Field of View 50cm, Z-direction coverage 22cm, Slice thickness 3mm, Reconstruction interval 3mm, Pitch 1, Matrix 512 x 512, Scan time Began 70 seconds after contrast media injection.

Image Analysis: A PACS system was used for the review and analysis of all MDCT images.

We analyzed possible predictors of lymph node metastases on preoperative CT images as follow: Lymph node diameter (shortest and longest axial diameter),The long-to-short axis (L/S) ratio, Presence of necrosis, conglomeration of lymph nodes, infiltration to adjacent soft tissue, laterality to the primary tumor and T stage of primary tumor, following the AJCC cancer staging manual, eighth edition. The largest diameters of each node in the axial and coronal planes were measured and defined as the longest diameter. The largest diameter perpendicular to the longest axial diameter was measured and defined as the shortest axial diameter. Slices for the measurement of the diameter of the lymph nodes were independently selected by each observer, and electronic calipers on the PACS system were used for such measurement.The L/S ratio was calculated by using the longest axial diameter/shortest axial diameter.The presence of necrosis was defined as central low density with irregular or rim- like enhancement of residual lymphatic tissue. The degree of necrosis was classified as none, present, or cystic (demonstrating a rim- like thin enhancing or imperceptible wall with >90%

of central low density) by visual analysis.Infiltration to adjacent soft tissue was defined as poorly defined nodal margins or soft-tissue infiltration or stranding of the muscles or fat in the neck.We performed a lymph nodal scoring model to all detected LNs on CT Images. The

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final diagnosis of LNs was confirmed based on Histological findings after surgery (30 LNs) or percutaneous US guided FNAC biopsies (46 LNs).

Statistical Analysis:

Data collected throughout history, basic clinical examination, laboratory investigations and outcome measures, entered and analyzed using Microsoft Excel software. Data were then imported into Statistical Package for Social Science (SPSS) version 22.0 (IBM, Armonk, New York) and PROC packages. According to the type of data qualitative represents as number and percentage, quantitative continues group represent by mean + SD. The following tests were used to test differences for significance, differences between frequencies (qualitative variables) and percentages were compared by Chi-square test. Differences between parameters quantitative independent groups by t test or Mann Whitney, p value was set at < 0.05 for significant results and < 0.001 for high significant results.

RESULTS

This study included 76 lymph nodes from 30 patients (17 males, 13 females) their age ranging from 25 to 81 years with mean age of 54.32 ± 13.38 years. There were 17 (56.7 %) male, 13 (43.3%) female. The most common age group is (55:>65 years) 10 patients (33.3%) and the least common age group is (75:>85 years) 1 patient (3.3%).

The most common site RT buccal region (5 cases), followed by Base of tongue (3 cases), followed by RT sided of tongue (cases 5), followed by LT sided of tongue (1 case), followed by Tip of nose (1case), followed by Lower lip (4 cases), followed by RT mandibular ramus (3cases), followed by Epiglottis, true ,false vocal cord, aryepiglottic fold (4 cases), followed by LT sided floor of mouth (2 cases), followed by LT external auditory meatus (1 case) and Swelling in posterior scalp. there were 10(16%) with T1, 34(52%) with T2, 22(36%) with T3, 10(16%) with T4.there were 42(56.7%) with T1 or T2 stage(score 0), 34(43.3%) with T3 or T4(score 1), 34(44.7%) with less than 1 Shortest axial diameter, 34(44.7%) with 1-2 Shortest axial diameter (score 1), 8(10.5%) with more than 2 Shortest axial diameter (score 4), 40(52.6%) with less than 1.5 L/S ratio (score 1), 36(47.4%) with more than 1.5 .5 L/S ratio (score 0), 34(44.7%) with necrosis (score3). there were 44 (57.9%) positive biopsy, the mean total score 3.16 (± 2.83 SD) with range (0-9). There were 7 LNs were categorized as score 1; 3 benign and 4 malignant, 7 LNs were categorized as score 2; 2 benign and 5 malignant, 10 LNs were categorized as score 3; 4 benign and 6 malignant, 9 LNs were categorized as score 4 4 benign and 5 malignant, 7 LNs were categorized as score 5; 3 was benign and 4 was malignant, 8 LNs were categorized as score 6; 2 was benign and 6 was malignant, 10 LNs were categorized as score 7, 5 was benign and 5 was malignant, 9 LNs were categorized as score 8; 4 was benign and 5 was malignant, 9 LNs were categorized as score 9; 3 was benign and 6 was malignant.

The Sensitivity was 87.50, Specificity 95.45, accuracy 92.1, PPV 91.3, NPV 93.3 at cutoff more than 3, true positive 42, true negative 28, false positive 4, false negative 2, PPV 91.3, NPV 93.3, Positive Likelihood Ratio 7.3 and Negative Likelihood Ratio 0.057.

Figure (1) showed that Distribution of the studied cases according to gender.

Figure (2) showed that Distribution of the studied cases according to age.

Figure (3) showed that ROC curve for total score to diagnose cervical LNs metastases.

Table (1) Demonstrate site and clinical presentation in our study.

Table (2) Distribution of the studied cases according to different parameters (n of L.Ns = 76).

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Table (3):Distribution of the studied cases according to total score and biopsy (n of L.N= 76).

Table (4) showed the validity of scoring system for diagnosis of cervical LNs metastases.

Table (5) showed that Final Diagnosis of LNs by scoring system stratified by histologic diagnosis

Figure (1): Distribution of the studied cases according to gender.

Figure (2): Distribution of the studied cases according to age

Table (1): Demonstrate site and clinical presentation in our study

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Site of lesion No of

cases Clinical presentation -RT buccal region

-Base of tongue -RT sided of tongue -LT sided of tongue -Tip of nose

-Lower lip

-RT mandibular ramus

-Epiglottis, True, False vocal cord, Aryepiglottic fold

-LT sided floor of mouth -LT external auditory meatus -posterior scalp

5 3 5 1 1 4 3 4 2 1 1

Pain, ulcer, swelling Lump seen in tongue Lump ,painful swelling Lump, painful swelling Ulcerating lesion Painful bleeding patch Large swelling Difficulty in breathing

Lump, difficult moving tongue Decrease hearing at LT side Swelling in posterior scalp

Table (2): Distribution of the studied cases according to different parameters (n of L.Ns = 76)

Score No. %

T stage (n =76)

T1 or T2 0 42 56.7

T3 or T4 1 34 43.3

Shortest axial diameter (n = 76)

<1 0 34 44.7

1 – 2 1 34 44.7

≥2 4 8 10.5

L/S ratio (n = 76)

<1.5 1 40 52.6

≥1.5 0 36 47.4

Necrosis (n = 76)

No 0 42 55.3

Yes 3 34 44.7

Table (3): Distribution of the studied cases according to total score and biopsy (n of L.N= 76)

No. %

Biopsy

Negative 32 42.1

Positive 44 57.9

Total score

Min. – Max. 0.0 – 9.0

Mean ± SD. 3.16 ± 2.83

Median (IQR) 2.0 (1.0 – 5.0)

Table (4): The validity of scoring system for diagnosis of cervical LNs metastases

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Parameters Scoring system

Cut-off > score 3

Number of true-positive findings 42

Number of false-negative findings 28

Number of false-positive findings 4

Number of true-negative findings 2

Accuracy (%) 92.1

Sensitivity (%) 87.50

Specificity (%) 95.45

Positive Predictive Value (%) 91.3

Negative Predictive Value (%) 93.3

Positive Likelihood Ratio 7.3

Negative Likelihood Ratio 0.057

Table(5): Final Diagnosis of LNs by scoring system stratified by histologic diagnosis

Score Total

(n=76)

Benign (n= 30)

Malignant (n= 46)

Score 1 7 3 4

Score 2 7 2 5

Score 3 10 4 6

Score 4 9 4 5

Score 5 7 3 4

Score 6 8 2 6

Score 7 10 5 5

Score 8 9 4 5

Score 9 9 3 6

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Figure(3) showed that ROC curve for total score to diagnose cervical LNs metastases

DISCUSSION

The study included 30 patients; they were 17 males and 13 females with their ages ranged from 25 to 81 years and their mean age of 54.32 ± 13.38 years. Our patients were referred from oncology department, Zagazig university hospitals as well as the outpatient clinic for Neck MDCT examination with intravenous contrast media during the period from November 2019 to April 2020.

Head and neck squamous cell carcinoma is a common, morbid and frequently lethal malignancy which arises from several anatomic sites. Tobacco exposure, alcohol dependence and infection with oncogenic virus are risk factors⁽⁶⁾.

Contrast-enhanced multidetector CT is the preferred imaging modality for staging of the neck and detection of lymph node metastasisin HNSCC^(7,8,9,10).

A comprehensive and systematic approach, based on features of lymph nodes (including diameters, shapes and presence of necrosis), combinations of those features ,and characteristics of primary tumor (such as T-stage or location) should be considered to determine the possibility of metastasis in daily practice ⁽⁴⁾.

Parameters that used in this model are T stage (1 or 2 take score 0, 3 or 4 take score 1), shortest axial diameter in cm(<1 cm take score 0, 1-2 cm take score 1, ≥2cm take score 4), L/S Ratio (<1.5 take score 1, ≥1.5 take score 0 )and necrosis (No: take score 0, Yes: take score 3)⁽³⁾.

Risk classification by total risk score⁽⁵⁾: 0-1(low risk ≤17% of metastases).

2-4: intermediate risk (17%-78% of metastases) 5-9: high risk ( ≥ 78% of metastases)

Total score

AUC 0.979

95%

C.I

LL 0.870 UL 1.000

P <0.001^*

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The study population was obtained from a historical cohort of consecutive patients who were newly diagnosed with HNSCC and underwent pretreatment contrast enhanced neck CT between November 2019 to April 2020. Our study included 30 HNSCC carcinoma (17 male (56.7%), 13 female (43.3%), the mean age 54.32±13.38 SD years with range 25-81 years ,and the median was 57 years). This mean that the high risk group to malignant changes was around 57 years.These results are compatible with that reported by (MS. chung et al., 2019) ⁽⁵⁾who included 191 patients (142 male,49 female ,mean age ,61.8±13.0 years range 28-91 years).

Squamous cell cancer of the oral cavity is the commonest malignant disease and accounts for 50-70% of total cancer mortality⁽¹¹⁾. The high incidence of oral cancer is due to tobacco chewing and smoking⁽¹²⁾.

Our study according to T stage of Primary tumor, the T stage of the primary tumor was stage I in 16%, stage II in 52%, stage III in 36%, stage IV in 16%.in comparison with (MS. Chung et al., 2019)⁽⁵⁾ In which The T stage of primary tumor was stage I in 25.7%, stage II in 33.5%, stage III in 29.3%,stage IV in 11.5%.

Risk scoring system have been used to stratify the risk of lymph node metastasis in various organs such as esophageal cancer, gastric cancer, melanoma, endometrial cancer and thyroid cancer⁽¹³⁾.

Our results agree with (MS Chung et al., 2019)⁽⁵⁾ the shortest axial diameter of lymph node and necrosis of lymph node demonstrated significant differences between benign and metastatic lymph node. Necrosis of lymph node showed the highest odds ratio of >15.

Imaging is playing a major role in the assessment of cervical lymphadenopathy. In head and neck malignancies, imaging can be helpful for staging. Imaging of the neck for the assessment of nodal metastasis can be used to detect occult metastases or assess operability of palpable metastasis.

Our study agree with (Castelijns JA et al., 2002)⁽¹⁵⁾ This study depend on Radiological criteria of L.N for detection of nodal metastasis such as increased size, a rounder shape, and the presence of noncontrast-enhancing parts or irregular contrast enhancement, caused by tumor necrosis.it has been shown that using the minimal diameter renders better results than the maximal diameter. The ratio of the longest diameter over the shortest diameter used in this study.

Yousem et al. ⁽¹⁴⁾ found that CT is more sensitive and accurate than MRI in detection of nodal necrosis.

Such et al., ⁽⁴⁾, Castelinjs et al., ⁽¹⁵⁾ .Almost all pre-existing modalities have variable diagnostic accuracy (sensitives range from 14% to 80% for CT and from 29% to 85% for MR Imaging specificities range from 80%to 100% for both CT and MR Imaging), our study showing diagnostic accuracy of CT is (sensitivity 87.50% and specificity 95.45%) using cut off value more than 3 points agree with results of Chung et al. ⁽⁵⁾ study.

For detecting node metastasis in HNSCC, our prediction model, which provides risk scores for the evaluation of lymph nodes, may provide objective evidence for diagnosis and might contribute to reduced interobserver variability.

Such et al., (2017)⁽⁴⁾ Many studies have described the diagnostic performance of CT for cervical lymph node metastasis, CT is a standardized objective imaging technique that is less operator dependent compared with us. In addition, CT provides detailed axial anatomic

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information systematically from the base of the skull to the mediastinum moreover, CT can evaluate lymph nodes in the retro-pharyngeal, retro-sternal, and mediastinal areas⁽¹⁶⁾as well as in situation that involve poor patient condition or low patient compliance.

Our scoring system has many advantages. It could provide a more targeted review for radiologists in an additional imaging study rather than focusing on high score (definite malignant) or low score (definite benign) lymph nodes, the additional evaluation should focus on lymph nodes with intermediate risk scores and it integrates variable preexisting CT criteria for lymph node metastasis and primary tumors in HNSCC⁽¹⁶⁾.

A B C

Figure (1): A 58-year-old male RT buccal SCC patient

(A) Axial CT view showing RT buccal mass measuring 3.3x4.9 cm.(white arrow),(B) Axial CT view showing RT LN level IB measuring 3X2 cm with necrosis ( score 6)(orange arrow),(C) Axial CT view showing RT LN level IB measuring 1.1X1.4 cm with necrosis(

score 6)(sky blue arrow),Nodes proved to be malignant

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Figure (2): A 48-year-old female RT sided anterior tongue SCC patient

(A) Axial CT view showing RT anterior soft tissue mass in tongue measuring 3x2 cm (white arrow),(B) Axial CT view showing RT LN level III measuring 1.2X1.5 cm with necrosis (score 5) (orange arrow),Node proved to be malignant

Limitation: 1^st some selection bias could have been introduced because our study was performed at a single place with a small number of patients, 2^nd we enrolled the patients who underwent a curative operation and 3^rdwe did not include patients who were treated with definite radiation therapy or concurrent chemo radiotherapy.

Conclusions

A simple 9- point risk scoring system using CT characteristics of lymph nodes and tumors for HNSCC could be feasible to stratify the risk of cervical lymph node metastasis with high diagnostic accuracy.

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