The impact of lymphovascular invasion on survival in oral carcinoma

doi:10.1016/j.oraloncology.2008.03.009

Oral Oncology

Volume 45, Issue 1, January 2009, Pages 10-15

https://doi.org/10.1016/j.oraloncology.2008.03.009 Get rights and content

Summary

Data was retrospectively analysed on 72 consecutive patients treated primarily with resection and concomitant neck dissection for intraoral carcinomas. Twenty prognostic variables were assessed by univariate analysis to assess their influence on survival. Seven variables were significant at the 5% level. Survival was negatively influenced by six tumour related factors, increasing T stage (P = 0.039), increasing N stage (P = 0.004), greater than two nodes histologically positive nodal disease (P = 0.017), tumour size >4 cm (P = 0.022), residual disease at the primary site (P = 0.012), extracapsular nodal spread (P = 0.01) and the one treatment related factor analysed, adjuvant radiotherapy (P = 0.039). Subsequent multivariate analysis was performed via the cox stepwise regression method to assess the influence on survival of all factors which achieved significance at the 20% level. There were only two variables which made a significant difference (P < 0.05) to the multivariate model. The presence of lymphovascular invasion (P = 0.015) and histological evidence of mandibular invasion (P = 0.047). Lymphovascular invasion appeared in the final model despite not achieving statistical significance at the 5% level on univariate analysis. A final cox survival model was constructed. The relative risk of death for those with cervical metastases (N2 and above) at diagnosis was 3.74 (P = 0.005). The addition of lymphovascular invasion to the cox model revealed an increase in the relative risk of death in the presence of lymphovascular invasion of 2.99 (P = 0.015). Patients with nodal negative disease and one single node positive provided the baseline risk as there was no significant difference between these two groups. The presence of histological evidence of lymphovascular invasion in oral carcinoma surgical specimens has a significant impact on survival outcome in oral carcinoma patients.

Introduction

In the search for prognostic factors in oral carcinoma many variables have been identified and can broadly be placed in the categories of tumour related, patient related and treatment related factors.¹

Prognosis in oral cancer is largely determined by tumour related factors. The tumour-node-metastasis (TNM) system of cancer classification recognises this fact.² However, this staging system does not incorporate histopathological factors at a time when they are increasingly recognised as being significant to prognosis.

The study aim was to relate histopathological features of primary oral carcinomas and neck dissection specimens to survival in oral carcinoma.

Section snippets

Materials and methods

The management principle of the two units from which the data for this study were sourced is identical. All operable patients with primary intraoral carcinomas are treated with surgery and concomitant neck dissection. Adjuvant radiotherapy is prescribed on pathological analysis of the surgical specimens, if there is evidence of close margins at the primary site (<5 mm), greater than one node positive, extracapsular spread or bulky metastatic disease in the neck dissection specimens.

Seventy-two

Statistical methods

The Cox regression method was used to investigate the effect of several variables at any given time. A forward stepwise Cox regression was performed for analysis of multiple variables which may have a prognostic impact on survival in this cohort of patients. Initial screening for prognostic variables was done by univariate analysis. Variables shown on univariate analysis to be prognostically statistically significant were entered into a multivariate analysis by the Cox proportional hazards

Outcome

There were ten local recurrences during the observation period, (14%) of whole group. Of the ten local recurrences, six were in the floor of mouth, two in the buccal mucosa, one in the left lateral tongue region and one in the hard palate Local recurrence occurred between a range of 68 and 1925 days (Mean 517 days). Consequently, 79% of all local recurrences presented clinically within 24 months of primary surgical treatment. There were 14 nodal recurrences (19%) of whole group. Nodal

Discussion

The natural history of tumours and the three key events which characterise malignancy are reflected in the TNM system.³ These are T is the ability to grow and locally invade, N is the ability to metastasize to regional draining lymphatics, and M is the ability to metastasize to distant sites.²

In relation to oral cavity tumours these three criteria are independent indicators of prognosis although they are intimately inter-related. Increasing size by T stage leads to an increase in the rate of

Conflict of Interest Statement

None declared.

References (30)

D. Hanahan et al.
The hallmarks of cancer
Cell
(2000)
S. Shingaki et al.
Impact of lymph node metastasis on the pattern of failure and survival in oral carcinomas
Am J Surg
(2003)
C.S. Woo et al.
Lymph node status combined with lymphovascular invasion creates a more powerful tool for predicting outcome in patients with invasive breast cancer
Am J Surg
(2002)
I.K. Kalnins et al.
Correlation between prognosis and degree of lymph node involvement in carcinoma of the oral cavity
Am J Surg
(1977)
C.D. Callery et al.
Changing trends in the management of squamous carcinoma of the tongue
Am J Surg
(1984)
J.A. Woolgar et al.
Cervical lymph node metastasis in oral cancer: the importance of even microscopic extracapsular spread
Oral Oncol
(2003)
J.A. Woolgar et al.
Survival and patterns of recurrence in 200 oral cancer patients treated by radical surgery and neck dissection
Oral Oncol
(1999)
A. Eckardt et al.
Recurrent carcinoma of the head and neck: treatment strategies and survival analysis in a 20-year period
Oral Oncol
(2004)
D. Franceschi et al.
Improved survival in the treatment of squamous carcinoma of the oral tongue
Am J Surg
(1993)
A.L. Carvalho et al.
Trends of oral and oropharyngeal cancer survival over five decades in 3267 patients treated in a single institution
Oral Oncol
(2004)

R.B. Bell et al.

Tongue cancer: Is there a difference in survival compared with other subsites in the oral cavity?

J Oral Maxillofac Surg

(2007)

A. Chandu et al.

Factors affecting survival in patients with oral cancer: an Australian perspective

Int J Oral Maxillofac Surg

(2005)

F. Janot et al.

Prognostic value of clinicopathological parameters in head and neck squamous cell carcinoma: a prospective analysis

Brit J Cancer

(1996)

C. Wittekind

R. Lindberg

Distribution of cervical lymph node metastases from squamous cell carcinoma of the upper respiratory and digestive tracts

Cancer

(1972)

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Stage of cancer at the time of the diagnosis is a key factor for the prognosis and the determination of appropriate treatment. Several cancer staging systems are used worldwide. The most useful staging system is the tumor, node and metastasis (TNM) staging system develop by the American Joint Committee on Cancer (AJCC) in collaboration with the Union for International Cancer Control (UICC) referred to as the AJCC TNM staging system. The AJCC TNM system classifies cancers by the size and extend of the primary tumor (T), involvement of regional lymph nodes (N) and the presence of distant metastases (M). AJCC and UICC periodically modify the AJCC TNM staging system according to newly acquired clinical, pathological and biological data improving understanding of cancer physiopathology. The 8th edition of AJCC TNM system is effective for cancer patients diagnosed on or after January 1, 2018. Here, we report the issues of the staging cancers of the oral cavity according to the 8th edition of AJCC TNM system. We focus on 2 new concepts defined in the 8th edition of AJCC TNM system: depth of invasion (DOI) and extranodal extension (ENE).
Does lymphovascular invasion predict survival in oral cancer? A population-based analysis
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To evaluate lymphovascular invasion as an independent predictor for overall survival in patients with oral cavity squamous cell carcinoma.
Retrospective cohort study.
Multi-center, population-based facilities reporting to the National Cancer Database registry.
The database was accessed to collect data on patients with oral cavity squamous cell carcinoma. A multivariate cox proportional hazards model was used to analyze the association between presence of lymphovascular invasion and overall survival.
16,992 patients met inclusion criteria. 3,457 patients had lymphovascular invasion. The mean follow-up was 32 ± 19 months. Lymphovascular invasion predicted reduced 2-year overall survival (relative hazard 1.29, 95% CI: 1.20, 1.38, p < 0.001) and 5-year overall survival (relative hazard 1.30, 95% CI: 1.23, 1.39, p < 0.001). LVI reduced overall survival in patients with squamous cell carcinoma of the oral tongue (HR: 1.27, 95% CI: 1.17, 1.39, p < 0.001), floor of mouth (HR: 1.33, 95% CI: 1.17, 1.52, p < 0.001) and buccal mucosa (HR: 1.44, 95% CI: 1.15, 1.81, p = 0.001). Patients with lymphovascular invasion treated with surgery plus post-operative radiotherapy had significantly improved survival compared to those who underwent surgery alone (relative hazard 1.79, 95% CI: 1.58, 2.03, p < 0.001), and patients treated with surgery + post-operative chemoradiotherapy had improved survival compared to those treated with surgery alone (relative hazard 2.0, 95% CI: 2.26, 1.79, p < 0.001).
Lymphovascular invasion is an important independent risk factor for decreased overall survival in oral cavity squamous cell carcinoma involving the oral tongue, floor of mouth and buccal mucosa subsites.
Prognostic value of lymphovascular and perineural invasion in squamous cell carcinoma of the tongue
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The objective of this study was to investigate the association between survival rate and lymphovascular invasion (LVI) and perineural invasion (PNI) in the tumor invasive front (TIF) of squamous cell carcinoma of the tongue (TSCC).
Seventy patients with TSCC were included. The retrospective analysis included demographic, clinical, and histopathologic data. Tissue blocks containing the TIF were stained with anti-α-smooth muscle actin and anti-S100 to detect LVI and PNI, respectively. Overall survival (OS) and disease-specific survival (DSS) were assessed using Pearson's chi-square test, Kaplan-Meier method, and Cox regression.
LVI and PNI were detected in 61.4% and 78.6% of the TSCC samples at the TIF, respectively. LVI and PNI were present in 54.3% of the cases and were associated with advanced clinical stage, lymph node resection, metastatic nodes, and lower survival (P < .05). The 5-year OS and DSS rates were 44% and 52%, respectively. Multivariate analysis showed that primary tumors >3.0 cm (hazard ratio = 4.29; P = .004) and a concomitant presence of LVI and PNI at the TIF (hazard ratio = 4.0; P = .012) were independent predictors for worse DSS.
LVI and PNI, identified by immunostaining at the TIF, are potential prognostic markers of TSCC.
Lymphovascular invasion as a prognostic tool for oral squamous cell carcinoma: a comprehensive review
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Oral cancer is the most common malignancy of the head and neck region, characterized by a poor prognosis. Novel prognostic markers are needed to better stratify these patients. Lymphovascular invasion (LVI) has been included in the eighth edition of the AJCC Cancer Staging Manual as an additional prognostic factor, but its influence on the recurrence risk and lymph node metastasis is relatively understudied. This is a comprehensive review of the literature on the clinical and prognostic role of LVI in oral cancer. A relevant search of the PubMed, Scopus, and Web of Science databases yielded 29 articles that satisfied the inclusion criteria. Findings indicated that LVI is an independent negative prognostic factor in oral cancer patients and appears to be associated with cervical lymph node metastasis and loco-regional recurrence. Notably, in oral tongue cancer, survival outcomes progressively worsen when LVI is associated with other adverse pathological features, especially in the early stages. Therefore, these patients could benefit from elective neck dissection and/or adjuvant therapy. The high variability of LVI prevalence hinders the comparison of literature results. Several methodological limitations were found to be present in the collected articles, including the lack of a rigorous definition for LVI, the difficult detection in routine histological section, the presence of potential confounders, the retrospective nature, and an inadequate sample size in most studies. Therefore, it is necessary to conduct prognostic studies using standardized methods to define and quantify LVI.
Impact of lymphovascular invasion in oral squamous cell carcinoma: A meta-analysis
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Lymphovascular invasion (LVI) has been reported as a predictor of prognosis in multiple cancers. The aim of this meta-analysis was to investigate the potential value of LVI as a prognostic predictor of oral squamous cell carcinoma (OSCC).
To identify relevant studies, PubMed, Embase, Web of Science, and Cochrane Library database were searched from inception to October 2020. All studies exploring the association of LVI with overall survival (OS), disease-specific survival (DSS), or disease-free survival (DFS) and lymph node metastasis (LNM) were identified.
Pooled odds ratios for LNM and hazard ratios for survival were calculated using fixed effects or random effects models. Thirty-six studies involving 17,109 patients with OSCC were included and further analyzed. The results showed that positive LVI was significantly associated with LNM and worse survival in patients with OSCC. Moreover, positive LVI was correlated with LNM in patients with early stage OSCC.
These findings indicate that LVI may serve as a prognostic predictor for the metastasis and prognosis of OSCC and could be considered a routine pathologic examination in clinical work.
The utility of postoperative radiotherapy in intermediate-risk oral squamous cell carcinoma
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The effectiveness of postoperative radiotherapy (PORT) in improving outcomes remains debatable for oral squamous cell carcinoma (OSCC) patients with pathological intermediate-risk factors (IRFs) after surgery. A retrospective analysis was conducted on 432 intermediate-risk OSCC patients defined by histological reporting of close margin (<5 mm), early nodal disease (pN1), depth of invasion/tumour thickness ≥5 mm, perineural invasion, and/or lymphovascular invasion. Outcomes measured were disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS). PORT was associated with an improvement in 5-year DFS on univariable analysis (80% vs 71%; P = 0.044), but this did not remain significant on multivariable analysis. PORT was not associated with differences in DSS or OS. The surgical salvage rate was similar in the PORT and surgery-only groups (41% vs 47%; P = 0.972). Perineural invasion was found to be an independent predictor of inferior DSS (hazard ratio (HR) 2.19), DFS (HR 1.89), and OS (HR 1.97). Significantly worse outcomes were observed for patients with ≥4 concurrent IRFs. The application of PORT was associated with lower rates of recurrence, but the benefit was less apparent on mortality. Patients with perineural invasion and multiple concurrent IRFs were found to be at greatest risk, representing a subset of intermediate-risk OSCC patients who may benefit from PORT.

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The impact of lymphovascular invasion on survival in oral carcinoma

Summary

Introduction

Section snippets

Materials and methods

Statistical methods

Outcome

Discussion

Conflict of Interest Statement

Cell

Am J Surg

Am J Surg

Am J Surg

Am J Surg

Oral Oncol

Oral Oncol

Oral Oncol

Am J Surg

Oral Oncol

J Oral Maxillofac Surg

Int J Oral Maxillofac Surg

Prognostic value of clinicopathological parameters in head and neck squamous cell carcinoma: a prospective analysis

Brit J Cancer

Distribution of cervical lymph node metastases from squamous cell carcinoma of the upper respiratory and digestive tracts

Cancer