|Year : 2019 | Volume
| Issue : 1 | Page : 61-65
Depth of tumor infiltration as a prognosticator in pT1-2 cN0 oral squamous cell carcinoma thereby need for elective neck dissection – A meta-analysis
Mohammad Akheel1, Rinku K George1, Amit Jain2, Qutubuddin Chahwala3, Ashmi Wadhwania4
1 Department of Oral and Maxillofacial Surgery, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India
2 Consultant Radiation Oncologist, CHL-CBCC Cancer Centre, Indore, India
3 Consultant Pathologist, CHL Hospitals, Indore, India
4 Consultant Oral and Maxillofacial Surgeon, Indore, India
|Date of Web Publication||9-Sep-2019|
Saveetha Dental College and Hospital, Chennai, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Aim: The aim of the study is to identify the cutoff value for depth of infiltration that predicts the risk of lymph node metastasis in the neck in surgically treated patients affected by pT1/pT2 cN0 oral squamous cell carcinoma (OSCC).
Materials and Methods: Meta-analysis of six articles, including 938 patients, was performed from a PubMed search of the last 15 years.
Results: The mean depth of infiltration in N0 neck was 4.42 mm, standard deviation (SD) 0.66 (95% confidence interval [CI], 3.89–4.95), while the mean depth of infiltration in N+ neck was 6.95 mm, SD 1.36 (95% CI, 5.86–8.04). One sample t-test done to analyze the level of significance between the cutoff depth of infiltration for N0 and N+ was found to be significant,P= 0.002. Receiver operating characteristic analysis was done to find the cutoff depth of infiltration in all N0 necks which was 4.5 mm with odds ratio 9.32, sensitivity of 84.7% in N+ necks which makes elective neck dissection an important surgical option for good prognosis of OSCC.
Conclusion: Tumor infiltration depth is an important prognosticator in pT1/pT2 cN0 necks. Tumors with depth of infiltration >4.5 mm radiologically or clinically should undergo an elective neck dissection to improve the prognosis of OSCC.
Keywords: HNSCC, LN dissection, neck dissection, oral squamous cell carcinoma, prognosis, T stage
|How to cite this article:|
Akheel M, George RK, Jain A, Chahwala Q, Wadhwania A. Depth of tumor infiltration as a prognosticator in pT1-2 cN0 oral squamous cell carcinoma thereby need for elective neck dissection – A meta-analysis. Cancer Res Stat Treat 2019;2:61-5
|How to cite this URL:|
Akheel M, George RK, Jain A, Chahwala Q, Wadhwania A. Depth of tumor infiltration as a prognosticator in pT1-2 cN0 oral squamous cell carcinoma thereby need for elective neck dissection – A meta-analysis. Cancer Res Stat Treat [serial online] 2019 [cited 2019 Nov 13];2:61-5. Available from: http://www.crstonline.com/text.asp?2019/2/1/61/266446
| Introduction|| |
Oral squamous cell carcinoma (OSCC) invades the surrounding tissues and metastasizes to regional lymph nodes, rarely developing distant metastases., In case of T3 and T4 tumors, there is a well-accepted role for neck dissection, but for the past five to six decades, there is a dilemma regarding the best approach to manage the neck in T1 and T2 tumors. Studies have compared elective neck dissection to therapeutic neck dissection. Occult metastases are present in 50% of OSCC of all stages even after clinical and radiological assessment by experienced head-and-neck oncologists., Addressing the neck electively at the time of resection of the primary tumor can be one of the surgical options to improve the prognosis of the patient. Moreover, performing a neck dissection in a clinically node negative (cN0) neck removes the natural barrier for tumor spread which is of particular importance. Elective neck dissection can be performed in cN0 neck when the chances of occult metastases are >20%. The pathological information obtained from the neck node status helps us to adequately stage the disease and plan further adjuvant treatment.,,
The unpredictable behavior of OSCC has focused on findings such as lymphovascular invasion, extracapsular spread, perineural invasion, and tumor infiltration depth., Recent literature suggests that depth of tumor infiltration is consistently associated with nodal metastasis and has an independent predictive value. The aim of this meta-analysis was to find the mean depth of infiltration for predicting the presence of lymph node metastasis in surgically treated patients with pT1/pT2 cN0 OSCC.
| Materials and Methods|| |
A PubMed electronic search for review articles was done with the following headings “depth of tumor infiltration,” “oral squamous cell carcinoma,” “prognosticator,” and “elective neck dissection” from period 2004–2019. Out of 10 articles obtained, 6 articles matched our inclusion criteria and were considered for our meta-analysis. Total number of patients included in the meta-analysis was 938 with histopathologically proven squamous cell carcinoma. All tumors included in the study were pathological T1 or T2 with cN0 neck. The depth of infiltration of the tumor was recorded pathologically after the resection. All the patients underwent elective neck dissection in cN0 neck.
The depth of tumor infiltration was defined as the maximum depth of tumor infiltration in millimeters below the mucosal surface. In case of an exophytic lesion, the reconstructed mucosal surface was used as a landmark. The nodal status of the patient was examined by clinical palpation of the neck and by other additional radiological investigations such as computed tomography (CT) and magnetic resonance imaging (MRI).
| Results|| |
A total of 938 patients with histopathologically proven OSCC were included in this meta-analysis. The lesions were pT1-2 cN0, and all the patients underwent elective neck dissection.
[Table 1] shows that the minimum depth of infiltration in N0 neck was 4 mm and the maximum was 5.49 mm and the mean depth of infiltration was 4.42 mm, standard deviation (SD) 0.66 (95% confidence interval [CI], 3.89–4.95). The minimum depth of infiltration in N+ neck was 5.5 mm and maximum was 8.49 mm and the mean depth of infiltration was 6.95 mm, SD 1.36 (95% CI, 5.86–8.04). One sample t-test was done to analyze the level of significance between the cutoff depth of infiltration for N0 and N+; which was found to be significant (P = 0.002).
|Table 1: Mean of cutoff depth of infiltration (mm) for pT1/pT2 oral squamous cell carcinomas, all of whom underwent elective neck dissection|
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Receiver operating characteristic curve analysis was done to find the cutoff depth of infiltration which was 4.5 mm with an odds ratio of 9.32 as shown in [Table 2], [Table 3], [Table 4] and [Figure 1] with a sensitivity of 84.7% and specificity of 63.8% in node-positive necks, and sensitivity of 73.2% and specificity of 75.5% which shows that a depth of tumor infiltration >4.5 mm requires elective neck dissection due to possibility for occult metastasis as given in [Table 5].
|Table 2: Receiver operating characteristic curve analysis to determine the cutoff value for the depth of infiltration (mm) with odds ratio|
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|Table 3: Coordinates of the curve demonstrating the cutoff depth of infiltration for node-negative and node-positive necks|
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|Table 4: Test result variable(s): Cutoff depth of infiltration (mm) for node-negative|
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|Figure 1: Receiver operating characteristic curve analysis which was done to find the cutoff depth of infiltration|
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|Table 5: Infiltration depth among the patients with node-negative and node-positive necks|
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[Table 3] shows that the value of sensitivity was >0.5 for positive cases; and the value of specificity was >0.5 for negative cases, thus implying that the tests used were appropriate, showing that the depth of infiltration is indeed a prognosticator. The data obtained were showing the appropriate desired values of sensitivity and specificity >0.5 for depth of infiltration >4.5 mm.
| Discussion|| |
This meta-analysis shows that the depth of tumor infiltration is an important prognosticator in OSCC for the presence of occult metastasis when the depth of tumor infiltration is >4.5 mm in pT1/pT2 cN0 tumors. As reported by Moore et al., the depth of tumor infiltration and tumor thickness are not the same, and a clear distinction must be made, even though many clinicians use these two terms synonymously. The depth of tumor infiltration denotes the extent of cancer growth into the tissue beneath the epithelial surface. In cases in which the epithelium is destroyed, some investigators reconstruct an imaginary surface line and measure from this line. However, the depth of tumor infiltration is sometimes expressed in terms of the microscopic, anatomic deep structures that are reached, rather than by referring to the objective micrometer measurements in millimeters. In this case, congruence among pathologists is less readily achieved because a series of subjective assessments are needed to determine the level of invasion.
Tumor thickness refers to the entire tumor mass for which an objective parameter is needed, which can be obtained using an ocular micrometer. The proximity to blood vessels and lymphatics is what determines an increased risk of nodal metastases developing in as much as it facilitates the tumor's ability to expand. Keski-Säntti et al. in 2007 assessed the predictive value of histopathologic parameters in early OSCC in 73 patients. They concluded that the depth of infiltration predicted occult nodal disease, but its value in clinical decision-making was limited because of poor specificity when using a cutoff value that offered reasonable sensitivity for finding patients with occult nodal disease. In our meta-analysis, the sensitivity was 84.7% in N+ necks with a cutoff depth of infiltration of 4.5 mm.
In 2012, Melchers et al. performed a classical study in 351 OSCC patients with pT1cN0 tumors, and they recommended an optimal cutoff for the prediction of the nodal status at a depth of 4.59 mm. They recommended an infiltration depth of >4 mm as an indication to perform a neck dissection. Balasubramanian et al. in 2014 compared the tumor thickness as a predictor of nodal metastases in cancers of the tongue and floor of mouth (FOM) subsites. They concluded that thin FOM tumors (2.1–4 mm) have a high rate of nodal metastases. They also suggested neck dissection in FOM tumors >2 mm thick and tongue tumors of >4 mm thickness. In 2013, Süslü et al. did a case series analysis of 138 patients and concluded that tumor thickness >8 mm and lymph node metastasis were independent predictors of worse survival in patients with SCC of the tongue. Since similar regional recurrence rates were observed in selective and radical neck dissections, supraomohyoid neck dissection was supported as a primary treatment for patients with cN0 tumors.
Garzino-Demo et al. in 2016 assessed the tumor infiltration depth in 150 cT1 cases of tongue and FOM. In 102 of the patients with depth <4 mm, the 5-year disease-specific survival was observed to be 95.15%, while it dropped to 72.27% for the 48 patients with invasion of >4 mm. Tarsitano et al. in 2016 conducted a retrospective longitudinal study to identify the cutoff value of infiltration depth for predicting the risk of lymph node metastasis of the neck in a well-defined population of surgically treated patients affected by stage T1 to T2 OSCC of the tongue. The mean infiltration depth of the node-negative group was found to be 2.4 mm which was substantially different from the mean value observed in the node-positive group at 5.5 mm. A meaningful cutoff was identified at an infiltration depth value of 4 mm.
The identification of a malignant node using the morphological modalities of CT, MRI, and ultrasound depends on the criteria of size, shape, and internal architecture., All three modalities have similar problems with respect to size and shape, and so their relative strengths and weaknesses depend on the ability to identify abnormalities of internal architecture such as nodal necrosis, extranodal neoplastic spread, nodal hilum, vascularity, and calcification.,, Nodal metastases are staged at the same time as the primary tumor, and hence, MRI or CT are employed most frequently. However, ultrasound has many additional advantages that improve the accuracy of detection of metastatic nodes. In addition, ultrasound is the best modality for performing image-guided biopsy. A recent meta-analysis showed that ultrasound-guided fine-needle aspiration cytology was the most accurate modality for detecting cervical lymph node metastases. Therefore, the additional use of ultrasound/ultrasound-guided biopsy appears justified in most patients, but because of resource implications, ultrasound may be targeted may be targeted at those patients who are likely to benefit the most, namely those who are candidates for surgery or observation.,,
After a reasonable number of studies and research by head-and-neck oncologists and pathologists, the most recent eight edition update of the American Joint Committee on Cancer Staging Manual in September 2016 has included tumor infiltration depth as a prognostic factor for tumor staging. The update includes tumors with greatest dimension of ≤2 cm but ≤5 mm of infiltration depth as T1. According to the updated staging system, tumors ≤2 cm but >5 mm or tumors >2 cm and ≤4 cm with infiltration depth and ≤10 mm have been upgraded as T2 tumors. Tumors with greatest dimension >2 cm and ≤4 cm and >10 mm infiltration depth or tumors >4 cm and ≤10 mm infiltration depth have been labeled as T3.
In summary, this meta-analysis shows that infiltration depth is an independent predictor for the presence of nodal metastasis in pT1/pT2 OSCC and that 4.5 mm is the optimal cutoff in cN0 necks. Hence, we recommend a good imaging modality preoperatively to identify the appropriate depth of tumor infiltration and to perform elective neck dissection; at least a supraomohyoid neck dissection when the depth of infiltration is >4.5 mm in cT1/cT2 tumors.
| Conclusion|| |
Tumor infiltration depth is an important prognosticator in pT1/pT2 cN0 necks. Tumor depth of infiltration >4.5 mm radiologically or clinically with cN0 neck must undergo an elective neck dissection; at least supraomohyoid neck dissection in an attempt to improve the prognosis.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Haddadin KJ, Soutar DS, Oliver RJ, Webster MH, Robertson AG, MacDonald DG, et al.
Improved survival for patients with clinically T1/T2, N0 tongue tumors undergoing a prophylactic neck dissection. Head Neck 1999;21:517-25.
Sobin L, Wittekind C. UICC TNM Classification of Malignant Tumours. 5th
ed. New York: Wiley & Sons; 1997.
Lydiatt DD, Robbins KT, Byers RM, Wolf PF. Treatment of stage I and II oral tongue cancer. Head Neck 1993;15:308-12.
Yuen AP, Wei WI, Wong YM, Tang KC. Elective neck dissection versus observation in the treatment of early oral tongue carcinoma. Head Neck 1997;19:583-8.
Bradley PJ, Ferlito A, Silver CE, Takes RP, Woolgar JA, Strojan P, et al.
Neck treatment and shoulder morbidity: Still a challenge. Head Neck 2011;33:1060-7.
Rennemo E, Zätterström U, Boysen M. Impact of second primary tumors on survival in head and neck cancer: An analysis of 2,063 cases. Laryngoscope 2008;118:1350-6.
Fasunla AJ, Greene BH, Timmesfeld N, Wiegand S, Werner JA, Sesterhenn AM. A meta-analysis of the randomized controlled trials on elective neck dissection versus therapeutic neck dissection in oral cavity cancers with clinically node-negative neck. Oral Oncol 2011;47:320-4.
Frech S, Hörmann K, Riedel F, Götte K. Lymphatic vessel density in correlation to lymph node metastasis in head and neck squamous cell carcinoma. Anticancer Res 2009;29:1675-9.
Longatto Filho A, Oliveira TG, Pinheiro C, de Carvalho MB, Curioni OA, Mercante AM, et al.
How useful is the assessment of lymphatic vascular density in oral carcinoma prognosis? World J Surg Oncol 2007;5:140.
Moore C, Kuhns JG, Greenberg RA. Thickness as prognostic aid in upper aerodigestive tract cancer. Arch Surg 1986;121:1410-4.
Barrera JE, Miller ME, Said S, Jafek BW, Campana JP, Shroyer KR. Detection of occult cervical micrometastases in patients with head and neck squamous cell cancer. Laryngoscope 2003;113:892-6.
Keski-Säntti H, Atula T, Törnwall J, Koivunen P, Mäkitie A. Elective neck treatment versus observation in patients with T1/T2 N0 squamous cell carcinoma of oral tongue. Oral Oncol 2006;42:96-101.
Melchers LJ, Schuuring E, van Dijk BA, de Bock GH, Witjes MJ, van der Laan BF, et al.
Tumour infiltration depth ≥4 mm is an indication for an elective neck dissection in pT1cN0 oral squamous cell carcinoma. Oral Oncol 2012;48:337-42.
Balasubramanian D, Ebrahimi A, Gupta R, Gao K, Elliott M, Palme CE, et al.
Tumour thickness as a predictor of nodal metastases in oral cancer: Comparison between tongue and floor of mouth subsites. Oral Oncol 2014;50:1165-8.
Süslü N, Hoşal AŞ, Aslan T, Sözeri B, Dolgun A. Carcinoma of the oral tongue: A case series analysis of prognostic factors and surgical outcomes. J Oral Maxillofac Surg 2013;71:1283-90.
Garzino-Demo P, Zavattero E, Franco P, Fasolis M, Tanteri G, Mettus A, et al.
Parameters and outcomes in 525 patients operated on for oral squamous cell carcinoma. J Craniomaxillofac Surg 2016;44:1414-21.
Tarsitano A, Del Corso G, Tardio ML, Marchetti C. Tumor infiltration depth as predictor of nodal metastasis in early tongue squamous cell carcinoma. J Oral Maxillofac Surg 2016;74:523-7.
van den Brekel MW, Runne RW, Smeele LE, Tiwari RM, Snow GB, Castelijns JA. Assessment of tumour invasion into the mandible: The value of different imaging techniques. Eur Radiol 1998;8:1552-7.
Daisne JF, Duprez T, Weynand B, Lonneux M, Hamoir M, Reychler H, et al.
Tumor volume in pharyngolaryngeal squamous cell carcinoma: Comparison at CT, MR imaging, and FDG PET and validation with surgical specimen. Radiology 2004;233:93-100.
King AD, Tse GM, Ahuja AT, Yuen EH, Vlantis AC, To EW, et al.
Necrosis in metastatic neck nodes: Diagnostic accuracy of CT, MR imaging, and US. Radiology 2004;230:720-6.
King AD, Tse GM, Yuen EH, To EW, Vlantis AC, Zee B, et al.
Comparison of CT and MR imaging for the detection of extranodal neoplastic spread in metastatic neck nodes. Eur J Radiol 2004;52:264-70.
Ying M, Ahuja A, Brook F, Metreweli C. Vascularity and grey-scale sonographic features of normal cervical lymph nodes: Variations with nodal size. Clin Radiol 2001;56:416-9.
Ahuja A, Ying M, King A, Yuen HY. Lymph node hilus: Gray scale and power Doppler sonography of cervical nodes. J Ultrasound Med 2001;20:987-92.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]