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Inicio Acta Otorrinolaringológica Española Predictors of locoregional recurrence in early stage buccal cancer with patholog...
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Vol. 69. Núm. 4.
Páginas 226-230 (Julio - Agosto 2018)
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Vol. 69. Núm. 4.
Páginas 226-230 (Julio - Agosto 2018)
Original article
DOI: 10.1016/j.otorri.2017.09.003
Acceso a texto completo
Predictors of locoregional recurrence in early stage buccal cancer with pathologically clear surgical margins and negative neck
Predictores de recidiva locorregional en cáncer temprano de mucosa bucal con márgenes quirúrgicos patológicos libres y cuello negativo
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Shakeel Uz Zaman
Autor para correspondencia
shakeek_120@hotmail.com

Corresponding author.
, Shakil Aqil, Mohammad Ahsan Sulaiman
Department of Otorhinolaryngology-Head and Neck Surgery, Liaquat National Hospital & Medical College, Karachi, Pakistan
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Tablas (3)
Table 1. Patient characteristics.
Table 2. Patterns of recurrence in patients according to the T classification.
Table 3. Univariate analysis of recurrence at endpoint.
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Abstract
Objective

To identify the significant predictors of locoregional recurrence in early stage squamous cell carcinoma (SCC) of buccal mucosa with pathologically clear surgical margins and negative neck.

Method

Seventy-three patients who underwent per oral wide excision and supraomohyoid neck dissection for early stage buccal SCC with clear surgical margins (>5mm margins each) and negative neck (N0) were included. None of the patients received postoperative radiotherapy or chemotherapy. Univariate and multivariate analyses were used to identify independent predictors of locoregional recurrence.

Results

Recurrence was observed in 22 of 73 (30%) cases. Twelve had local, seven had regional and three developed locoregional recurrences. Both univariate and multivariate analyses demonstrated that lymphovascular invasion (LVI) and non-T4 muscular invasion (non-T4MI) were independent predictors affecting locoregional control.

Conclusion

Lymphovascular invasion (LVI) and non-T4 muscular invasion (non-T4MI) significantly increased the locoregional recurrence rate in early stage buccal SCC with clear surgical margins and negative nodal status. Adjuvant treatment with either radiation or chemoradiation should be considered when one or both of these factors present.

Keywords:
Mouth neoplasms
Margins of excision
Neck dissection
Recurrence
Resumen
Objetivo

Identificar los predictores significativos de recidiva locorregional en el carcinoma de células escamosas (CCS) en estadios iniciales de la mucosa buccal, con los márgenes quirúrgicos patológico libres y el cuello negativo.

Método

Se incluyeron en el estudio 73 pacientes sometidos a extirpación tumoral y disección supraomoioidea de cuello con cáncer bucal en estadios iniciales con márgenes quirúrgicos libres (margen de 5mm cada uno) y cuello negativo (N0). Ninguno de los pacientes recibió radioterapia postoperatoria o quimioterapia. Se utilizaron análisis univariantes y multivariantes para identificar los factores predictivos independientes de recidiva locorregional.

Resultados

La recidiva se observó en 22 de 73 casos (30%). Doce tenían recidivas locales, 7 regionales y 3 desarrollaron recidivas locorregionales. Tanto los análisis univariantes como multivariantes demostraron que la invasión linfovascular (LVI) y la invasión muscular no T4 (non-T4MI) fueron predictores independientes que afectaron al control locorregional.

Conclusión

La LVI y la non-T4MI aumentaron significativamente la tasa de recurrencia locorregional en el CCS bucal precoz con márgenes quirúrgicos libres y estado nodal negativo. El tratamiento adyuvante con radiación o quimiorradiación debe considerarse cuando se presentan uno o ambos de estos factores.

Palabras clave:
Neoplasias de la boca
Márgenes de la excisión
Disección del cuello
Recidiva
Texto completo
Introduction

Early stage (I and II) buccal squamous cell carcinoma (SCC) is mainly treated by wide local excision of tumor +/− neck dissection. Even after surgery, there is high locoregional failure rate which results in increase morbidity to patient.1 Several adverse features result in this elevated failure rate, including extracapsular spread of node, positive margin, involvement of more than two nodes, lymphovascular invasion (LVI), perineural invasion (PNI), and tumor thickness of >4mm,2,3 so presence of any of these factors are indicator for adjuvant treatment in the form of radiation or chemoradiation which is also mentioned in National Comprehensive Cancer Network (NCCN) Head and Neck cancers guidelines.4

There are few reports in the literature analyzing the prognostic predictors for early stage buccal SCC particularly from our region. The aim of this study was to identify the significant predictors of locoregional recurrence in a cohort of previously untreated early stage SCC of buccal mucosa with pathologically clear surgical margins and negative neck.

Materials & methods

We retrospectively reviewed the medical records & pathology reports of patients with buccal SCC who received treatment in Liaquat National Hospital Karachi from January 2007 to December 2011. Patients fulfilling the following criteria were included in our study: (1) Biopsy proven buccal SCC treated with per oral excision; (2) T1 or T2 clinical and pathological stage; (3) clear surgical margins (>5mm margins each) in pathology specimen; (4) clinically and pathologically no evidence of neck node involvement (N0). In our institution all stage I (T1N0M0) and stage II (T2N0M0) buccal lesions are treated with wide local excision of tumor and ipsilateral supraomohyoid (level I–III) neck dissection. None of the patients received postoperative radiotherapy or chemotherapy. Patients were excluded if: (1) Buccal lesions involving commissure, lip, upper alveolus, mandible, floor of mouth, tongue or retromolar trigone; (2) received treatment from outside; (3) recurrent tumors; (4) distant metastasis; (5) lost to follow-up (minimum follow-up of 5 years). All tumors were staged according to the TNM staging system, as proposed by the 2002 American Joint Committee on Cancer (AJCC).

The primary endpoint of the study was local, regional or locoregional recurrence. Local recurrence was defined as the occurrence of the same malignancy arising from the original tumor beds as proven by incisional or excisional biopsy. Regional recurrence referred to neck metastases proven by fine needle aspiration cytology or biopsy of lymph nodes in dissected or un-dissected levels. Locoregional recurrence when tumor appears in both primary site and neck.

Data was analyzed by using SPSS version 21. Descriptive statistics were computed for quantitative and qualitative variables. Univariate and multiple logistic regression analysis were used to determine association of variables with recurrence. All odds ratios were reported with a 95% confidence interval. p-value <0.05 was considered to be statistically significant.

Results

A total of 73 patients were found eligible for the study. Patient characteristics are listed in Table 1. Mean age of patients was 49.00±12.76 years (range, 20–86 years). Seventy one percent cases were aged >40 years. Out of 73 patients, 56 (76.7%) were males while rest of 17 (23.3%) were females. There was equal number of right and left sided tumors while 68.5% cases had moderately differentiated tumors. Fourteen (19.2%) buccal lesions involved lymphovascular invasion (LVI); eight (11%) perineural invasion (PNI); and sixteen (21.9%) non-T4 muscular invasion (non-T4MI). No case in our study group had dysplasia in resection margins. Majority (76.7%) of buccal tumors had thickness of ≥5mm. Most of the patients had exposure to various oral risk factors i.e. tobacco (35/73), betel quid chewing (26/73), smoking (6/73) and alcohol (3/73), but all of them abandoned their addictions post surgery.

Table 1.

Patient characteristics.

  n (%) 
Characteristics  73 
Age (years)
≤40  21 (28.8) 
>40  52 (71.2) 
Gender
Male  56 (76.7) 
Female  17 (23.3) 
Side of lesion
Right  37 (50.7) 
Left  36 (49.3) 
T-stage
T1  35 (47.9) 
T2  38 (52.1) 
Grading
Well differentiated  12 (16.4) 
Moderately differentiated  50 (68.5) 
Poorly differentiated  11 (15.1) 
Lymphovascular invasion
Yes  14 (19.2) 
No  59 (80.8) 
Perineural invasion
Yes  8 (11) 
No  65 (89) 
Non-T4 muscular invasion
Yes  16 (21.9) 
No  57 (78.1) 
Thickness(mm)
<5mm  17 (23.3) 
≥5mm  56 (76.7) 
Recurrence
Yes  22 (30.1) 
No  51 (69.9) 

Tumors recurred in 22/73 (30.1%) patients within the follow-up period. In most patients (12/22, 54.5%), tumor recurred locally while seven had regional and three cases had locoregional recurrence (Fig. 1). All regional recurrences occurred in same side of the neck, four at level IV and three at level II. In locoregional failure, all three cases had neck metastasis at level IV. No patients developed distant metastasis in follow-up. Sixteen patients (72.7%) had recurrence within the first 2 years of primary treatment. The pattern of failure among the different T classifications is shown in Table 2.

Figure 1.

Patterns of recurrence.

(0,04MB).
Table 2.

Patterns of recurrence in patients according to the T classification.

  T1  T2 
No recurrence  26  25 
Local recurrence 
Regional recurrence 
Locoregional recurrence 
Total  35  38 

Univariate analysis revealed that LVI (p=0.000) and non-T4MI (p=0.000) were significantly associated with locoregional recurrences (Table 3). Age, gender, side of lesion, T-stage, grade, PNI and thickness were not significantly associated with locoregional recurrence. Multivariate analysis also revealed that only LVI (OR=31.51, p=0.000) and non-T4MI (OR=41.92, p=0.001) were independent factors for locoregional recurrence.

Table 3.

Univariate analysis of recurrence at endpoint.

  No. of recurrence  Odds ratio  95% CI*  p-value 
Age (years)
≤40  12/21  57.1  2.25  0.77–6.54  0.137 
>40®  39/52  75  –  – 
Gender
Male  16/56  28.6  0.733  0.23–2.31  0.598 
Female®  6/17  35.3  –  – 
Side of lesion
Right  9/37  24.3  0.569  0.20–1.56  0.275 
Left®  13/36  36.1  –  – 
T-stage
T1  9/35  25.7  0.666  0.24–1.83  0.431 
T2®  13/38  34.2  –  – 
Grading
Well differentiated  2/12  16.7  0.167  0.02–1.14  0.068 
Moderately differentiated  14/50  28  0.324  0.08–1.23  0.099 
Poorly differentiated®  6/11  54.5  –  – 
Lymphovascular invasion
Yes  11/14  78.6  16.00  3.81–67.18  0.000 
No®  11/59  18.6  –  – 
Perineural invasion
Yes  1/8  12.5  0.299  0.03–2.59  0.273 
No®  21/65  32.3  –  – 
Non-T4 muscular invasion
Yes  13/16  81.3  23.11  5.45–97.85  0.000 
No®  9/57  15.8  –  – 
Thickness
<5mm  5/17  29.4  0.956  0.29–3.13  0.941 
≥5mm®  17/56  30.4  –  – 

®Reference category.

*

CI confidence interval.

Discussion

Squamous cell carcinoma of the buccal mucosa is the most common form of oral cancer in Southeast Asian countries.5 Two earlier studies concluded that involved margins and neck nodes involvement were the most significant prognostic factors in early stage buccal cancer.6,7 However, the importance of others predictors are insufficient. The main reason is the heterogeneity in the past study groups, which included tumors with different margins (clear/close/involved) and nodal statuses (N0 and N+). The sample population in this study was relatively homogenous with respect to margins and nodal status.

In our study, most of the cases were >40 years of age corresponding to study from India.8 Male was the dominant gender in our research comparable to work done by Hakeem et al.9 T2 lesions were greater than T1 in our series, similar to study from Iyer et al.8 We found that more than sixty percent of our patients presented with moderately differentiated tumors. This was almost analogous to what was reported in the literature.10 LVI and PNI were higher than those reported in earlier study (LVI=19% vs. 2.5%, PNI=11% vs. 6%).9 Non-T4MI tumors (22%) were lesser than Huang et al.,11 (27%) but their work included tumors from other oral cavity sub-sites as well. In present study majority of cases had tumor thickness >5mm comparable to analysis done by O’brien et al.12

The overall locoregional recurrence rate was 30% in this study group comparable to other studies.6,9 Half of these tumors recurred locally analogous to work done by Diaz et al.13 In this series, most of the recurrences found in T2 lesions (19 cases) with more than 70% overall failure in first 2 years of life which is corresponding to literature8 and hold the same view that vigilant follow-up in the first 2 years after surgical treatment is necessary as majority of the recurrences occurred during that period.

In the current study, we identified two independent prognostic factors i.e. LVI and non-T4MI for early stage buccal cancers. Other important predictors that are T-stage, grade, PNI and thickness were not associated with recurrence in both univariate and multivariate analyses. Ghoshal et al.14 and Lin et al.1 reported T-stage and grade as independent factor, finding not established in our series. Similarly PNI correlated with failure of treatment in previous works,10,15,16 but current study failed to show a predictive relationship. Several investigations have revealed correlation between the tumor thickness and locoregional control. Work done by Sheahan et al.17 and Kane et al.18 showed tumor thickness ≥5mm had increased chances of occult neck node in early buccal SCC with poor prognosis later on. Our 17/22 recurrences also had tumor thickness of 5mm or more but it was not statistically significant. Two studies from Taiwan10,11 and one from China19 showed that LVI & non-T4MI were significant predictors for locoregional failure, findings consistent with our case series.

Conclusion

Our results demonstrate that lymphovascular invasion (LVI) and non-T4 muscular invasion (non-T4MI) significantly increased the locoregional recurrence rate in early stage buccal SCC with clear surgical margins and negative nodal status. Adjuvant treatment with either radiation or chemoradiation should be considered when one or both of these factors present.

Ethical approval

This retrospective study was in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

For this type of study, formal consent is not required.

Funding statement

This research received no grant from any funding agency in the public, commercial or not-for profit sectors.

Conflict of interest statement

None of the authors of this paper has a financial or personal relationship with other people or organizations that could inappropriately influence or bias the content of the paper.

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