Lymphovascular Space Invasion Predicts Locoregional Tongue Cancer Recurrence

The increased risk of locoregional recurrence in patients with node-negative tongue cancer who display lymphovascular space invasion might warrant aggressive adjuvant treatment

medwireNews: The presence of lymphovascular space invasion (LVSI) could trigger use of more aggressive adjuvant therapy in patients who undergo resection for node-negative oral tongue cancer, researchers suggest.

“LVSI seems to be associated with local and regional recurrence, worse survival, without an increase in distant metastasis”, say Richard Cassidy, from Winship Cancer Institute of Emory University in Atlanta, Georgia, USA, and co-workers.

“Given the locoregional recurrence risk in patients with node-negative oral tongue cancers treated with definitive surgery, the presence of LVSI warrants consideration of adjuvant radiation to the primary site and draining lymphatics, which ideally should be investigated in a prospective setting”, they recommend.

The team reviewed the outcomes of 180 patients who were followed up for a median of 4.9 years after undergoing definitive surgery between 2003 and 2013 plus adjuvant radiotherapy or chemoradiotherapy as indicated by standard clinical and pathological markers.

The majority (70%) of patients had T1 disease, 20.6% T2, 5.6% T3 and 3.8% T4a. All were classified as cN0 and 62% underwent elective neck dissection and received confirmation of pathologically (p)N0 status.

In all, 20% of the patients had LVSI. Three-year rates of locoregional control were significantly poorer for patients with this biomarker than without, at 38.8% versus 81.9%.

Multivariate analysis, adjusting for race, perineural invasion, depth of invasion, use of elective neck dissection and receipt of adjuvant treatment, revealed that the presence of LVSI significantly predicted both poorer local control (odds ratio [OR]=0.24) and locoregional control (OR=0.06).

By contrast, receipt of adjuvant radiotherapy was a significant predictor of improved local and locoregional control, giving ORs of 4.30 and 7.74, respectively. Neck dissection was also a significant positive prognostic factor for locoregional control (OR=2.99).

“This suggests that even with appropriately delivered adjuvant therapy, the use of elective neck dissection is beneficial in node-negative oral tongue cancers”, the authors write in JAMA Otolaryngology – Head & Neck Surgery.

Thirty of the 42 patients who experienced failure at the primary site achieved durable control with salvage surgery, as did 22 of the 33 patients who underwent salvage surgery for neck failure. This gave an ultimate locoregional control rate of 83.3%. On adjustment, LVSI and close margins significantly predicted a poorer ultimate rate, with ORs of 0.22 and 0.24, respectively.

Three-year rates of overall survival were significantly lower in patients with LVSI than their counterparts without LVSI, at 71.3% versus 90.3%. On multivariate analysis, LVSI and age above 44 years were the only significant risk factors to predict poor overall survival, with hazard ratios of 2.20 and 4.38, respectively.

The researchers note that just one of the five patients who developed metastatic disease had LVSI.


Cassidy RJ, Switchenko JM, Jegadeesh N, et al. Association of lymphovascular space invasion with locoregional failure and survival in patients with node-negative oral tongue cancers. JAMA Otolaryngol Head Neck Surg; Advance online publication 12 January 2017. doi:10.1001/jamaoto.2016.3795 

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