The Prognostic Value of Lymph Node Burden in Oral Cavity Cancer: Systematic Review and Meta-Analysis.

OBJECTIVES: Lymph node burden has been proposed to estimate the cumulative adverse effect of nodal metastasis. In this study, a meta-analysis was conducted to evaluate the prognostic value of lymph node burden in oral cavity squamous cell carcinoma. STUDY DESIGNS: Systemic review and meta-analysis. METHODS: PubMed, EMBASE and the Cochrane Library as well as manual searches were performed until April 2020. The adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of overall survival, disease-specific survival, and disease-free survival were extracted and pooled. RESULTS: Eleven included studies were published between 2009 and 2019. The cumulative number of patients was 20,607 (range 35-14,554). Extranodal extension was adjusted or evaluated in all of the studies. The meta-analysis indicated that a higher lymph node burden was significantly related to worse overall survival (HR 2.62, 95% CI 2.12-3.25), worse disease-specific survival (HR 3.14, 95% CI 1.85-5.33) and worse disease-free survival (HR 2.30, 95% CI 1.62-3.26). The highest hazard ratio was observed when the cutoff value was 3 for overall survival, 3 for disease-specific survival, and 4 for disease-free survival. The hazard ratio showed an upward trend before the cutoff value of 3 but no significant incremental change when the cutoff exceeded 3. CONCLUSIONS: In oral squamous cell carcinoma, lymph node burden is an independent prognosticator for survival outcomes. However, more prospective or high-quality studies are required to determine the optimal cutoff. LEVEL OF EVIDENCE: NA Laryngoscope, 132:88-95, 2022.

The role of postoperative radiotherapy in pN1 oral cavity cancer without extranodal extension.

BACKGROUND: The administration of postoperative radiotherapy remains controversial in pN1 oral cavity cancer patients without extranodal extension. The aim is to determine whether postoperative radiotherapy reduces the neck recurrence rate and improves the survival outcomes of pN1 patients. METHODS: This study consecutively enrolled 1056 patients with newly diagnosed oral squamous cell carcinoma who underwent tumor wide excision and neck dissection from September 2002 to November 2019. One hundred two pN1 patients without extranodal extension were eligible for analysis. Then, a subgroup analysis of 40 patients was performed after patients with other adverse risk factors (positive margins, close margins, lymphovascular invasion, perineural invasion, tumor depth ≥ 10 mm, and poor histological differentiation) were excluded. RESULTS: Of the 102 eligible pN1 patients, 26 patients received surgery alone, and 76 received postoperative radiotherapy. No significant differences were observed in the neck recurrence rate (7.7% vs. 15.8%, p = 0.30). Similarly, in patients without other adverse risk factors, no significant differences were observed in the neck recurrence rate (5% vs. 20%, p = 0.15) between surgery alone group and postoperative radiotherapy group. Moreover, no significant difference was found in the neck recurrence-free survival rate, overall survival, and disease-specific survival (77.1% vs. 52.5%, p = 0.42, 83.5% vs. 64.5%, p = 0.81, and 88.2% vs. 67.9%, p = 0.34, respectively). CONCLUSION: Postoperative radiotherapy did not significantly decrease the probability of neck recurrence and survival outcomes in pN1 patients without extranodal extension. Radical surgery alone may be considered sufficient treatment for pN1 patients without other adverse risk factors.

Surgical Margins Status and Prognosis after Resection of Oral Cavity Squamous Cell Carcinoma: Results from a Taiwanese Nationwide Registry-Based Study.

(1) Background: The optimal cutoff value that maximizes the prognostic value of surgical margins in patients with resected oral cavity squamous cell carcinoma has not yet been identified. (2) Methods: Data for this study were retrieved from the Taiwan Cancer Registry Database. A total of 13,768 Taiwanese patients with oral cavity squamous cell carcinoma were identified and stratified according to different margin statuses (0, 0.1-4 and > 4 mm). The five-year local control, disease-specific survival and overall survival rates were the main outcome measures. (3) Results: The 5-year local control, disease-specific survival and overall survival rates of patients with close margins (0 and 0.1-4 mm) were significantly lower than those observed in patients with clear margins (> 4 mm; all p values < 0.001). In multivariate analysis, margin status, depth of invasion and extra-nodal extension were identified as independent adverse prognostic factors for 5-year local control. (4) Conclusions: A thorough assessment of surgical margins can provide a reliable prognostic prediction in patients with OCSCC. This has potential implications for treatment approaches tailored to the individual level. The achievement of clear margins (>4 mm) should be considered a key surgical goal to improve outcomes in this patient group.

Association of subcutaneous and visceral adipose tissue with overall survival in Taiwanese patients with bone metastases - results from a retrospective analysis of consecutively collected data.

BACKGROUND: Growing evidence indicates that measures of body composition may be related to clinical outcomes in patients with malignancies. The aim of this study was to investigate whether measures of regional adiposity-including subcutaneous adipose tissue index (SATI) and visceral adipose tissue index (VATI)-can be associated with overall survival (OS) in Taiwanese patients with bone metastases. METHODS: This is a retrospective analysis of prospectively collected data. We examined 1280 patients with bone metastases who had undergone radiotherapy (RT) between March 2005 and August 2013. Body composition (SATI, VATI, and muscle index) was assessed by computed tomography at the third lumbar vertebra and normalized for patient height. Patients were divided into low- and high-adiposity groups (for both SATI and VATI) according to sex-specific median values. RESULTS: Both SATI (hazard ratio [HR]: 0.696; P<0.001) and VATI (HR: 0.87; P = 0.037)-but not muscle index-were independently associated with a more favorable OS, with the former showing a stronger relationship. The most favorable OS was observed in women with high SATI (11.21 months; 95% confidence interval: 9.434-12.988; P<0.001). CONCLUSIONS: High SATI and VATI are associated with a more favorable OS in Taiwanese patients with bone metastases referred for RT. The question as to whether clinical measures aimed at improving adiposity may improve OS in this clinical population deserves further scrutiny.

Prognostic significance of pretreatment neutrophil-to-lymphocyte ratio in older patients with metastatic cancer.

BACKGROUND: Treatment options for older patients with malignancies remain suboptimal. An accurate prognostic stratification could inform treatment decisions, which can potentially improve patient outcomes. Here, we sought to investigate whether the neutrophil-to-lymphocyte ratio (NLR) may have prognostic significance in patients with metastatic malignant tumors, with a special focus on older individuals. METHODS: We retrospectively reviewed the clinical records of 3981 patients with histology-proven metastatic cancer who underwent radiotherapy between 2000 and 2013. The pretreatment NLR was determined within 7 days before treatment initiation. Patients aged ≥65 years were considered as older. We analyzed the prognostic significance of NLR for overall survival (OS) across all age groups. RESULTS: Compared with their younger counterparts, older patients showed a higher NLR (P < 0.001) and a lower OS (P < 0.001). Multivariate analysis revealed that a pretreatment NLR below the median was an independent favorable predictor of OS in both older (hazard ratio [HR]: 0.669, 95.0% CI: 0.605-0.740; P < 0.001) and younger patients (HR: 0.704; 95.0% CI: 0.648-0.765; P < 0.001). Regardless of age, patients who underwent systemic therapy showed more favorable OS, especially when NLR was low. In the older subgroup, the OS of patients with a low pretreatment NLR who did not undergo systemic therapy and of those with high pretreatment NLR who underwent systemic therapy was similar. CONCLUSION: A low pretreatment NLR predicts a more favorable OS in older patients with metastatic cancer. The most favorable OS was observed in patients with a low pretreatment NLR who received systemic therapy.

Roles of preoperative C-reactive protein are more relevant in buccal cancer than other subsites.

BACKGROUND: C-reactive protein (CRP) is an early marker for inflammation, and a relationship between serum CRP levels and survival in oral cancer has been demonstrated previously. In this study, we investigated the roles of CRP in different oral cancer subsites. METHODS: Three hundred and forty-three oral squamous cell carcinoma patients between June 1999 and March 2015 were retrospectively reviewed. Serum CRP levels were measured preoperatively. RESULTS: The elevation of CRP levels (≥5.0 mg/L) was significantly correlated with pathologic tumor status, pathologic nodal status, nodal extracapsular spread, tumor stage, skin invasion, tumor depth (≥10 mm), and bone invasion. The correlation between elevation of CRP and clinicopathologic factors was more evident in the buccal cancer compared to other tumor subsites. The disease-free survival and overall survival correlation was significant in buccal cancer (p = 0.003 and p < 0.001) but not in tongue cancer (p = 0.119 and p = 0.341) or other oral cancer subsites (p = 0.246 and p = 0.696). CONCLUSIONS: Preoperative serum CRP level was a prognosticator in oral squamous cell carcinoma, and its effect was more prominent in buccal cancer that occurs more frequently in areca-quid (AQ) endemic regions.