Early-stage Oral Cavity Squamous Cell Research Articles

Depth of invasion as an independent prognostic factor in early-stage oral cavity squamous cell carcinoma

PurposeTo determine the significance of depth of invasion as a predictor of recurrence and mortality in tongue and non-tongue early-stage oral cavity squamous cell carcinoma patients treated with surgery and no postoperative radiotherapy. Materials and methods344 patients with oral cavity squamous cell carcinoma from 2005 to 2022 at a tertiary academic medical center were reviewed. Patients were included if they had newly diagnosed, previously untreated T1-T2N0 disease treated with surgery alone that was observed within a follow-up of 5 years. For each patient, anatomic site of oral cavity squamous cell carcinoma was categorized as either tongue or non-tongue. Cox proportional hazards regression analyses were performed to determine the association of depth of invasion with recurrence and mortality, with anatomic site, smoking status, and age at biopsy as covariates. Model assumptions were tested by statistical and graphical evaluation using Schoenfeld residuals. ResultsOf 108 patients with T1-T2N0 disease, 78 (72.2 %) had tongue disease, and 30 (27.8 %) had non-tongue disease. Median follow-up was 18.2 months (range, 0.01–58.2 months). In the Cox proportional hazards models, with adjustment for anatomic site and other covariates, depth of invasion positively predicted recurrence (HR 1.16, 95 % CI: 1.01–1.32, p = 0.034) and death (HR 1.42, 95 % CI: 1.11–1.83, p = 0.006). ConclusionsDepth of invasion is an independent predictor of recurrence and death across early-stage tongue and non-tongue squamous cell carcinoma. Therefore, depth of invasion may indicate a need for more aggressive treatment than surgery alone, such as postoperative radiotherapy, even in the absence of other adverse features on pathology within the early-stage population.

Is elective neck dissection justified in cT2N0M0 oral cavity cancer defined according to the AJCC eighth edition staging system?

The current NCCN guidelines recommend considering elective neck dissection (END) for early-stage oral cavity squamous cell carcinoma (OCSCC) with a depth of invasion (DOI) exceeding 3 mm. However, this DOI threshold, determined by evaluating the occult lymph node metastatic rate, lacks robust supporting evidence regarding its impact on patient outcomes. In this nationwide study, we sought to explore the specific indications for END in patients diagnosed with OCSCC at stage cT2N0M0, as defined by the AJCC Eighth Edition staging criteria. We examined 4723 patients with cT2N0M0 OCSCC, of which 3744 underwent END and 979 were monitored through neck observation (NO). Patients who underwent END had better 5-year outcomes compared to those in the NO group. The END group had higher rates of neck control (95% vs. 84%, p < 0.0001), disease-specific survival (DSS; 87% vs. 84%, p = 0.0259), and overall survival (OS; 79% vs. 73%, p = 0.0002). Multivariable analysis identified NO, DOI ≥5.0 mm, and moderate-to-poor tumor differentiation as independent risk factors for 5-year neck control, DSS, and OS. Based on these prognostic variables, three distinct outcome subgroups were identified within the NO group. These included a low-risk subgroup (DOI <5 mm plus well-differentiated tumor), an intermediate-risk subgroup (DOI ≥5.0 mm or moderately differentiated tumor), and a high-risk subgroup (poorly differentiated tumor or DOI ≥5.0 mm plus moderately differentiated tumor). Notably, the 5-year survival outcomes (neck control/DSS/OS) for the low-risk subgroup within the NO group (97%/95%/85%, n = 251) were not inferior to those of the END group (95%/87%/79%). By implementing risk stratification within the NO group, we found that 26% (251/979) of low-risk patients achieved outcomes similar to those in the END group. Therefore, when making decisions regarding the implementation of END in patients with cT2N0M0 OCSCC, factors such as DOI and tumor differentiation should be taken into account.

Significance of Worst Pattern of Invasion-5 in Early-Stage Oral Cavity Squamous Cell Carcinoma

BackgroundThere is an ongoing need to identify pathologic prognosticators in early-stage oral cavity squamous cell carcinoma (OCSCC) to aid selection of patients who may benefit from adjuvant treatment. The objective of this study was to evaluate the prognostic ability of worst pattern of invasion-5 (WPOI-5) defined by the presence of satellite nodules, extratumoural perineural invasion (PNI) and/or extratumoural lymphovascular space invasion (LVI) in low-stage, node negative OCSCC.MethodsThis was a retrospective study of 160 patients with T1/T2N0 tumours staged using TNM7 treated surgically. Histology of the primary tumour was re-reviewed as appropriate to assess for the presence of WPOI-5 parameters. Univariate and multivariate analysis assessing impact of pathological features on survival outcomes was performed.ResultsOn univariate analysis, WPOI-5 and its 3 constituent components of satellite nodules, extratumoural PNI and extratumoural LVI were all significantly associated with disease-specific survival (DSS) and overall survival (OS). On multivariate analysis, satellite nodules (odds ratio 6.61, 95% CI 2.83–15.44, p < 0.0001) and extratumoural LVI (odds ratio 9.97, 95% CI 2.19–45.35, p = 0.003) were independently associated with OS. Postoperative radiotherapy (odds ratio 0.40, 95% CI 0.19–0.87, p = 0.02) and non-tongue subsite (odds ratio 3.03, 95% CI 1.70–5.39, p = 0.0002) were also significantly associated with OS on multivariate analysis.ConclusionSatellite nodules and extratumoural LVI correlated significantly with survival outcomes in our early-stage OSCC cohort. Further study is required to investigate the benefit of adjuvant treatment in these cases and to ascertain if WPOI-5 parameters including satellite nodules should be mandatory reporting data elements.

Re-examining predictors of pathologic lymph node positivity in clinically node negative oral cavity cancer

BackgroundElective lymph node dissection (ELND) is performed for many early-stage oral cavity squamous cell carcinomas (OCSCC) with clinically negative necks (cN0), often guided by depth of invasion (DOI). However, DOI is less validated in non-tongue OC sites, and often correlates with other adverse features. We sought to evaluate the utility of DOI versus other factors for independently predicting pathologic lymph node positivity (pN+) in patients with cN0 OCSCC. MethodsPatients with cN0 OCSCC diagnosed from 2010 to 2015 undergoing primary surgery were identified in the National Cancer Data Base. Results5060 cN0 OCSCC patients met inclusion criteria. The presence of lymphovascular invasion (LVI) was the strongest independent predictor of pN+ (odds ratio [OR] = 4.27, 95% confidence interval [CI] 3.36–5.42, P < 0.001). High histologic grade also strongly predicted pN+ (OR 3.33, 95% CI 2.20–4.60, P < 0.001). DOI had no association with the likelihood of pN+ among all OCSCC patients, but was predictive among patients within the oral tongue subset (OR 2.01, 95% CI 1.08–3.73, P = 0.03 for DOI > 20 mm vs. DOI: 2.0–3.99 mm). ConclusionLVI and grade are the strongest independent predictors of pN+ in cN0 OCSCC. Contrary to prior studies, DOI was not found to be a predictor of pN+ among patients with cN0 OCSCC. However, DOI was a predictor of pN+ or the oral tongue subset, albeit still less strongly than LVI or grade. These findings could potentially be used to better identify a subset of cN0 OCSCC patients who could be considered for omission of ELND in future studies.

Positive margin and advanced depth of invasion as the indicators for assessing the necessity of adjuvant chemoradiotherapy in early-stage oral cavity squamous cell carcinoma.

e18052 Background: Adjuvant therapy was indicated for patients with a high risk of disease progression after curative therapy, and RTOC 9501/EORTC 22931 were the landmark studies for assessing the necessity of adjuvant therapy in oral cavity squamous cell carcinoma (OCSCC). However, the role of adjuvant therapy in early-staging OCSCC, which was redefined by the 8th edition American Joint Committee on Cancer (AJCC) staging system, was unknown. Methods: A total of 485 early-staging OCSCC patients (pT1-2N0) diagnosed between Jan 2010 and Dec 2019 were retrospectively enrolled. All of them were newly diagnosed and reevaluated to meet the criteria of the 8th edition AJCC staging system. Adjuvant therapy was discussed and concluded in the combined conference of the head and neck multidisciplinary team at Chung Shan Medical University Hospital. And the enrolled patients were divided into the groups with or without adjuvant therapy. The effectiveness of adjuvant therapy and prognostic factor for locoregional recurrence-free survival (LRFS) were analyzed. Results: Nearly one-sixth (16.1%, 78/485) of the enrolled patients received adjuvant therapy. The patients with adjuvant therapy were worse in pathologic T staging ( P &lt; 0.001), histologic grade ( P &lt; 0.001), and pathologic features (depth of invasion [DOI] &gt; 4mm, P &lt; 0.001; perineural invasion, P &lt; 0.001) than those without. Positive margin and advanced DOI ( &gt; 4mm) were the independent factors for LRFS. Adjuvant therapy did not improve LRFS that the 3-year LRFS of the patients with or without adjuvant therapy were 79.7% and 81.5%, respectively ( P = 0.718)(hazard ratio [HR], 95% confidence interval [CI]: 1.10 [0.67-1.80]). However, adjuvant chemoradiotherapy (CRT) indeed prolonged LRFS in some subgroups, such as those with positive margin or advanced DOI (the subgroup with positive margin, 3-year LRFS of those with or without adjuvant therapy, 100% and 58.8%, HR[95% CI]: 0.04[0.00-267.330]; the subgroup with advanced DOI, 3-year LRFS, 83.3% and 73.1%, HR[95% CI]: 0.48[0.16-2.01]). In addition to positive margin, advanced DOI was the most critical correlation coefficient factor among the pathologic features, including pathologic T staging, perineural invasion, lymphovascular invasion, poorly differentiated, and close margin. For the patients eligible for evaluation, forty percent (40.1%, 180/439) of the patients were diagnosed with positive margins or advanced DOI and these patients might be considered to receive adjuvant CRT in the future. Conclusions: Positive margin and DOI were the most important indicators to evaluate the necessity of adjuvant CRT in early-staging OCSCC. Future warranted studies were needed.

Adjuvant radiotherapy mitigates impact of perineural invasion on oncologic outcomes in early-stage oral cavity squamous cell carcinoma. A multi-institutional analysis of 557 patients

ObjectivesUnderstand the prognostic impact of perineural invasion (PNI) in early-stage oral cavity squamous cell carcinoma (OCSCC). Assess the influence of adjuvant radiotherapy on outcomes of patients with PNI-positive early-stage OCSCC. Materials and MethodsRetrospective seven-institution cohort study including patients with pathologic T1-2 N0-1 OCSCC who underwent primary surgery with negative margins. Outcomes included disease-free survival (DFS) and locoregional control (LRC). Cox proportional hazards models were used to evaluate oncologic outcomes. Interaction terms were introduced to assess relationships between PNI and adjuvant radiotherapy. ResultsAmong 557 patients (mean (SD) age 61.0 (13.9), 47.2% female, 66.6% pathologic T1, 93.5% pathologic N0), 93 had PNI-positive tumors, among which 87.1% underwent neck dissection and 39.6% received radiotherapy. On multivariable analysis, PNI was associated with lower DFS and LRC. Adjuvant radiotherapy was not associated with improved outcomes on multivariable analysis of the entire cohort. However, among patients with PNI-positive tumors, adjuvant radiotherapy significantly decreased hazard for DFS. ConclusionAmong patients with low-risk, early-stage OCSCC, PNI was associated with worse DFS and LRC. In patients with PNI-positive tumors, adjuvant radiotherapy lowered hazard for DFS on multivariable analysis. These data support using adjuvant radiotherapy for patients with early-stage OCSCC with PNI.

Indications for elective neck dissection in cT1N0M0 oral cavity cancer according to the AJCC eight edition: A nationwide study

ObjectivesAccording to the NCCN guidelines, there is weak evidence to support the use of elective neck dissection (END) in early-stage oral cavity squamous cell carcinoma (OCSCC). We sought to examine the indications for END in patients with cT1N0M0 OCSCC defined according to the AJCC Staging Manual, Eight Edition. MethodsOf the 3886 patients diagnosed with cT1N0M0 included in the study, 2065 underwent END and 1821 neck observation. ResultsThe 5-year outcomes for patients who received END versus neck observation before and after propensity score matching (n = 1406 each) were as follows: neck control, 96 %/90 % (before matching), p < 0.0001; 96 %/90 % (after matching), p < 0.0001; disease-specific survival (DSS), 93 %/92 % (before matching), p = 0.0227; 93 %/92 % (after matching), p = 0.1436. Multivariable analyses revealed that neck observation, depth of invasion (DOI) > 2.5 mm, and poor differentiation were independent risk factors for 5-year outcomes. Upon the application of a scoring system ranging from 0 (no risk factor) to 3 (presence of the three risk factors), the following 5-year rates were observed: neck control, 98 %/95 %/84 %/85 %; DSS, 96 %/93 %/88 %/85 %; and overall survival, 90 %/86 %/79 %/59 %, respectively (all p < 0.0001). The survival outcomes of patients with scores of 0 and 1 were similar. The occult metastasis rates in the entire study cohort, DOI > 2.5 mm, and poor differentiation were 6.8 %/9.2 %/17.1 %, respectively. ConclusionBecause all patients who received neck observation had a score of 1 or higher, END should be performed when a DOI > 2.5 mm or poorly differentiated tumors are present. Under these circumstances, 48.6 % (1888/3886) of cT1N0M0 patients may avoid END without compromising oncological outcomes.

Relationship between lymph nodes examined and survival benefits with postoperative radiotherapy in oral cavity squamous cell carcinoma patients with stage T1-2N1M0.

BackgroundThis study aims to explore the relationship between the lymph nodes examined and survival benefits of postoperative radiotherapy in oral cavity squamous cell carcinoma patients with stage T1-2N1M0.MethodsThis study retrieved patients who underwent dissection of the primary site and neck lymph nodes for pT1-2N1M0 oral cavity squamous cell carcinoma without adverse nodal features from the Surveillance, Epidemiology, and End Results database from 2004 to 2015. Propensity score matching analysis was conducted, and the best cutoff value of the lymph nodes examined was determined by X-tile. Cancer-specific survival was the primary outcome. Univariable and multivariable analyses were performed to assess the relation between postoperative radiotherapy and cancer-specific survival, adjusting for other prognostic factors.ResultsA total of 469 patients were finally enrolled according to our exclusion criteria, and then 119 pairs of patients were matched by propensity score matching analysis. The best cutoff value of the lymph nodes examined was determined by X-tile, stratifying patients into lymph nodes examined ≤16 group and lymph nodes examined >16 group. For the whole matched cohort, the choice of postoperative radiotherapy had no correlation with other factors (all p’s > 0.05), and postoperative radiotherapy made no contribution to a better survival outcome for patients (p = 0.289). After stratified by the lymph nodes examined, in the lymph nodes examined ≤16 group, significantly improved CSS was found for those who undertook postoperative radiotherapy compared to those who just received surgery (unadjusted hazard ratio, 0.541; 95% confidence interval, 0.333–0.878; p = 0.013).ConclusionsOur study revealed that pT1-2N1M0 oral cavity squamous cell carcinoma patients were more likely to benefit from postoperative radiotherapy when unsatisfactory neck dissection was conducted, indicating that the number of lymph nodes examined might be a factor when clinicians do therapeutic planning for early-stage oral cavity squamous cell carcinoma patients.

Impact of Histologic Risk Factors on Recurrence Rates for Oral Cavity Squamous Cell Carcinoma.

This study assesses the impact of adverse histologic risk factors including worst pattern of invasion (WPOI), predominant pattern of invasion (PPOI), tumor budding, and tumor infiltrating lymphocytes (TILS), on risk of recurrence in patients with early-stage Oral Cavity Squamous Cell Carcinoma (OCSCC). Retrospective chart review was performed at a single institution to identify patients with OCSCC who underwent surgical excision. Inclusion criteria included T1-T2 stage disease based on AJCC seventh edition guidelines, no cervical lymph node involvement, no perineural invasion (PNI), no lymphovascular invasion (LVI), no post-operative adjuvant radiation therapy, and cancer involving only the oral tongue or floor of mouth. Patients were excluded if they had positive final margins. A subset of 35 patients were selected for additional histologic review to determine WPOI, PPOI, TB, and TILS. Bivariable and multivariable cox analysis were performed to determine variables associated with recurrence. One hundred and sixty-one patients met criteria and were included in the analysis. Variables that were significantly associated with recurrence on bivariable analysis included tumors with high risk PPOI (groups 4 and 5; P = .021), TB with 10 or more buds (P = .021), T-stage (P = .001), neck dissection (P = .03), and depth of invasion (DOI) >4 mm (P = .044). Multivariable cox proportional hazards found T-stage (HR: 6.40; 95% CI 1.67, 24.50; P = .007), neck dissection (HR: 0.23; 95% CI 0.07, 0.82; P = .023), and TBs (HR: 1.17; 95% CI 1.05, 1.30; P = .006) to be most predictive of recurrence. TB is a strong predictor of recurrence. WPOI, PPOI, and TILS were not statistically significant risk factors for recurrence.

Development and Validation of Machine Learning Models for Predicting Occult Nodal Metastasis in Early-Stage Oral Cavity Squamous Cell Carcinoma

Given that early-stage oral cavity squamous cell carcinoma (OCSCC) has a high propensity for subclinical nodal metastasis, elective neck dissection has become standard practice for many patients with clinically negative nodes. Unfortunately, for most patients without regional metastasis, this risk-averse treatment paradigm results in unnecessary morbidity. To develop and validate predictive models of occult nodal metastasis from clinicopathological variables that were available after surgical extirpation of the primary tumor and to compare predictive performance against depth of invasion (DOI), the currently accepted standard. This diagnostic modeling study collected clinicopathological variables retrospectively from 7 tertiary care academic medical centers across the US. Participants included adult patients with early-stage OCSCC without nodal involvement who underwent primary surgical extirpation with or without upfront elective neck dissection. These patients were initially evaluated between January 1, 2000, and December 31, 2019. Largest tumor dimension, tumor thickness, DOI, margin status, lymphovascular invasion, perineural invasion, muscle invasion, submucosal invasion, dysplasia, histological grade, anatomical subsite, age, sex, smoking history, race and ethnicity, and body mass index (calculated as weight in kilograms divided by height in meters squared). Occult nodal metastasis identified either at the time of elective neck dissection or regional recurrence within 2 years of initial surgery. Of the 634 included patients (mean [SD] age, 61.2 [13.6] years; 344 men [54.3%]), 114 (18.0%) had occult nodal metastasis. Patients with occult nodal metastasis had a higher frequency of lymphovascular invasion (26.3% vs 8.1%; P < .001), perineural invasion (40.4% vs 18.5%; P < .001), and margin involvement by invasive tumor (12.3% vs 6.3%; P = .046) compared with those without pathological lymph node metastasis. In addition, patients with vs those without occult nodal metastasis had a higher frequency of poorly differentiated primary tumor (20.2% vs 6.2%; P < .001) and greater DOI (7.0 vs 5.4 mm; P < .001). A predictive model that was built with XGBoost architecture outperformed the commonly used DOI threshold of 4 mm, achieving an area under the curve of 0.84 (95% CI, 0.80-0.88) vs 0.62 (95% CI, 0.57-0.67) with DOI. This model had a sensitivity of 91.7%, specificity of 72.6%, positive predictive value of 39.3%, and negative predictive value of 97.8%. Results of this study showed that machine learning models that were developed from multi-institutional clinicopathological data have the potential to not only reduce the number of pathologically node-negative neck dissections but also accurately identify patients with early OCSCC who are at highest risk for nodal metastases.

The impact of sentinel lymph node biopsy on the quality of life in patients with oral cavity squamous cell carcinoma

IntroductionSentinel lymph node biopsy is a proven method for staging the neck in patients with early oral cavity squamous cell carcinoma because it results in less comorbidity than the traditional method of selective neck dissection, with the same oncological results. However, the real effect of that method on the quality of life of such patients remains unknown. ObjectiveThe present study aimed to evaluate the quality of life of patients with oral cavity squamous cell carcinoma T1/T2N0 submitted to sentinel lymph node biopsy compared to those that received selective neck dissection. MethodsCross-sectional study including 24 patients, after a 36 month follow-up, 15 of them submitted to the sentinel lymph node biopsy and 9 to selective neck dissection. All patients answered the University of Washington quality of life questionnaire. ResultsThe evaluation of the questionnaires showed a late worsening of the domains appearance (p=0.035) and chewing (p=0.041), as well as a decrease of about 10% of general quality of life (p=0.025) in patients undergoing selective neck dissection ​​in comparison to those undergoing sentinel lymph node biopsy. ConclusionPatients with early-stage oral cavity squamous cell carcinoma undergoing sentinel lymph node biopsy presented better late results of general quality of life, mainly regarding appearance and chewing, when compared to patients submitted to selective neck dissection.

Comparison of Intra-Operative Depth of Invasion Measurement by Frozen Section with Post-Operative Histopathology in Patient of Oral Cavity Squamous Cell Carcinoma.

Depth of Invasion (DOI) is an important and independent predictor for occult metastasis and recurrence. AJCC staging system (8th edition) has incorporated DOI in the staging of oral cancers. It is an essential parameter in deciding elective neck dissection. We hereby conducted a study to determine the accuracy of DOI in the frozen section as compared to the histological section in patients with T1N0 oral squamous cell carcinoma. This study was conducted over a period of 45months in a tertiary care hospital. 31 patients with diagnosed Oral SCC and with T1N0 were enrolled. The intra-operative frozen section was done DOI was measured as per Cap protocol and compared with the DOI in the histopathological section. Strong correlation was found between DOI measured by frozen section and permanent section (r = 0.998; 95% CI, 0.999-0.997). The paired t test showed a mean difference of 0.0066mm (95% CI, -0.0103-0.02346mm; P = 0.096) between frozen section and permanent section. DOI measured was slightly higher in frozen section however this difference was neither statically nor clinically significant.This study shows the accuracy of frozen specimens in determining tumor DOI in T1N0M0 in oral cavity squamous cell carcinoma. Intraoperative DOI along with other factors may be used to determine the need for END (elective neck dissection) in early-stage oral cavity squamous cell carcinoma andthus avoid a staged operation or over- or under-treatment of the neck.

New Developments in Imaging for Sentinel Lymph Node Biopsy in Early-Stage Oral Cavity Squamous Cell Carcinoma.

Simple SummaryIn early-stage (cT1-2N0) oral cancer, occult lymph node metastases are present in 20–30% of patients. Accordingly, accurate staging of the clinically negative cervical nodal basin is warranted in these patients. Sentinel lymph node biopsy has proven to reliably stage the clinically negative cervical nodal basin in early-stage oral cancer. However, due to the limited resolution of conventional sentinel lymph node imaging, occult lymph node metastasis may be missed in particular circumstances. Therefore, technical developments are necessary to bring the diagnostic accuracy of sentinel lymph node biopsy, in early-stage oral cancer, to a higher level. This review evaluates novel sentinel lymph node imaging techniques for early-stage oral cancer, such as MR lymphography, CT lymphography, PET lymphoscintigraphy and contrast-enhanced lymphosonography. Their reported diagnostic accuracy is described and their relative merits, disadvantages and potential applications are outlined.Sentinel lymph node biopsy (SLNB) is a diagnostic staging procedure that aims to identify the first draining lymph node(s) from the primary tumor, the sentinel lymph nodes (SLN), as their histopathological status reflects the histopathological status of the rest of the nodal basin. The routine SLNB procedure consists of peritumoral injections with a technetium-99m [99mTc]-labelled radiotracer followed by lymphoscintigraphy and SPECT-CT imaging. Based on these imaging results, the identified SLNs are marked for surgical extirpation and are subjected to histopathological assessment. The routine SLNB procedure has proven to reliably stage the clinically negative neck in early-stage oral squamous cell carcinoma (OSCC). However, an infamous limitation arises in situations where SLNs are located in close vicinity of the tracer injection site. In these cases, the hotspot of the injection site can hide adjacent SLNs and hamper the discrimination between tracer injection site and SLNs (shine-through phenomenon). Therefore, technical developments are needed to bring the diagnostic accuracy of SLNB for early-stage OSCC to a higher level. This review evaluates novel SLNB imaging techniques for early-stage OSCC: MR lymphography, CT lymphography, PET lymphoscintigraphy and contrast-enhanced lymphosonography. Furthermore, their reported diagnostic accuracy is described and their relative merits, disadvantages and potential applications are outlined.

Older patients with early-stage oral cavity squamous cell carcinoma: outcomes for elderly patients aged 70 years or older

Background: The standard of care in operable oral cavity cancer is curative surgery followed by adjuvant therapy. However, adjuvant management of elderly patients with early-stage oral cavity squamous cell carcinoma (OCSCC) remains controversial. This study aims to identify predictors that will guide the adjuvant management in these patients.

Incidence of Micrometastasis and Isolated Tumour Cells in Clinicopathologically Node-Negative Head and Neck Squamous Cell Carcinoma.

Occult neck node metastasis in head and neck squamous cell carcinoma (HNSCC) in the form of micrometastasis and isolated tumour cell (ITC) often goes unnoticed in the routine pathological examination. This limitation can be overcome by using serial sectioning and immunohistochemistry for detection of micrometastasis and ITC in clinically and pathologically node-negative neck. The primary objective was to determine the incidence of micrometastasis and ITC in the selective neck dissection specimen, whereas to determine the levels of lymph nodes involved, depending upon the site of primary tumour, was the secondary objective. Lymph nodes from selective neck dissection specimen were subjected to serial sectioning and immunohistochemistry with pan-cytokeratin marker. Incidence of micrometastasis and ITC, site and stage of primary tumours and level of lymph nodes involved were determined. In total, 8.8% patients in the study got upstaged after serial sectioning and immunohistochemistry. Tongue and lower alveolar primaries showed the presence of micrometastasis and ITC in neck nodes. All the primary tumours were of pT1 stage. Level IB and II lymph nodes were primarily involved. Micrometastasis and isolated tumour cells are found in approximately 9% of cases of early-stage oral cavity squamous cell carcinoma. The predictive factors and clinical significance are still unknown. More prospective trials are required to solve this evolving aspect of HNSCC.

Elective Neck Dissection Versus Wait-and-Watch Policy for Oral Cavity Squamous Cell Carcinoma in Early Stage: A Systematic Review and Meta-Analysis Based on Survival Data

Whether elective neck dissection (END) should be adopted for patients with clinically early-stage (cT1-2N0M0) oral cavity squamous cell carcinoma (OCSCC) remains debated. The aim of this systematic review was to compare the survival benefit of END with that of the wait-and-watch policy (WW) for patients with early-stage OCSCC based on survival data. According to the inclusion criteria, an exhaustive search for eligible studies was conducted. The study inclusion and data extraction were performed by 2 reviewers independently. The risk of bias was assessed in duplicate using the Risk Of Bias In Nonrandomized Studies of Interventions instrument. The hazard ratio (HR) of the time-to-event data was extracted or estimated. RevMan 5.3 and STATA 15.1 were adopted for data synthesis. Of the 35 studies that were included, only 5 were assessed as having a low risk of bias. Results of the meta-analyses showed END could significantly decrease neck recurrence (relative risk=0.45; confidence interval [CI], 0.35-0.59; P<.00001) and improve disease-free survival (HR=0.55; CI, 0.42-0.71; P<.00001), overall survival (HR=0.75; CI, 0.64-0.86; P<.0001), and disease-specific survival (HR=0.76; CI, 0.61-0.94; P=.01) compared with WW for patients with cT1-2N0. The subgroup analysis showed that END could decrease neck recurrence (P<.00001) and improve disease-free survival (P=.001) for patients with early-stage tongue cancer and that supraomohyoid neck dissection could decrease neck recurrence (P=.02). For patients with cT1N0, END could significantly decrease the proportion with neck recurrence (P=.0008) and improve disease-free survival (P=.0003), but the difference between overall survival and disease-specific survival did not achieve significance. END can decrease recurrence and improve survival time for patients with early-stage OCSCC. More high-quality studies are needed to make a solid conclusion, especially for patients with cT1N0M0.

Intraoperative Depth of Invasion Is Accurate in Early-Stage Oral Cavity Squamous Cell Carcinoma

Depth of invasion (DOI) is one predictor of nodal metastasis in oral cavity squamous cell carcinoma (OCSCC) and can facilitate the decision to complete an elective neck dissection (END) in early-stage disease with a clinically negative neck. The purpose of this study was to investigate the accuracy of DOI in intraoperative frozen specimens for T1N0 oral OCSCC. To compare the accuracy of DOI in frozen versus permanent specimens, we completed a prospective, blinded study of 30 patients with cT1N0 OCSCC who presented between October 2016 and December2017. DOI in frozen specimens was 96.8% accurate in predicting the need for END with a sensitivity of 90.9%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 95.2%. A strong correlation was found between DOIs in frozen and permanent specimens measured by head and neck (HN) pathologists (r=0.96; 95% confidence interval [CI], 0.93 to 0.97), between HN pathologists using frozen specimens (r=0.98; 95% CI, 0.95 to 0.99) and permanent specimens (r=0.95; 95% CI, 0.91 to 0.98), and in DOIs in frozen specimens communicated intraoperatively versus measured by HN pathologist 1 (r=0.93; 95% CI, 0.86 to 0.97) and HN pathologist 2 (r=0.95; 95% CI, 0.89 to 0.98). Only 1 patient who did not undergo an END based on frozen specimens was undertreated owing to upgrading of the DOI in permanent specimens. DOI in intraoperative frozen sections has an accuracy of 96.8% and may be reliably used as a clinical tool to determine the need for END in early-stage OCSCC.

Depth of invasion alone as a prognostic factor in low-risk early-stage oral cavity carcinoma.

To evaluate the significance of increasing depth of invasion (DOI) as the sole risk factor for recurrence in patients with low-risk early-stage oral cavity squamous cell carcinoma (OCSCC). We retrospectively reviewed 560 patients with OCSCC treated at our institution between 2003 and 2013. Patients were included if they had low-risk early-stage OCSCC treated with surgical resection ± neck dissection and no adjuvant therapy. Low risk was defined as absence of positive or close margins, lymphovascular invasion, perineural invasion, and positive lymph nodes. Patients with tumor (T)3-T4 disease were excluded. Pathology specimens were independently re-reviewed by two board-certified pathologists to confirm proper measurement of DOI. Kaplan-Meier and Cox proportional hazards regression analyses were performed to identify factors predictive for recurrence as well as progression-free survival (PFS) and overall survival (OS). A total of 126 patients with low-risk early-stage T1-2N0 OCSCC were included. Median follow-up time was 42.5 months and median DOI was 4 mm. There was no significant difference in incidence of local (P = 0.95), regional (P = 0.81), or distant recurrence (P = 0.96) among patients with DOI < 4 mm versus ≥4 mm. On multivariable analysis, DOI was significant for both PFS (P = 0.03) and OS (P = 0.002). In this study, we show that in the absence of other high-risk pathologic features, DOI ≥ 4 mm does not portend for increased incidence of local, regional, or distant relapse in patients treated with surgery alone; however, increasing DOI is a marker for worse PFS and OS in patients with low-risk, early-stage OCSCC. 4 Laryngoscope, 129:2082-2086, 2019.

Risk of submandibular gland metastasis in early-stage oral cavity cancer: A national multicentric study

Background: The objective of this study was to evaluate the safety of preserving the submandibular gland in early-stage oral cavity cancer. Materials and Methods: We retrospectively collected the data for all patients who present with early-stage oral cavity cancer and underwent local wide excision with concomitant neck dissection over 8 years from 2008 to 2016 at two tertiary oncology centers in Saudi Arabia. Results: Forty-seven patients, comprising 26 males (55.3%) and 21 females (44.7%), were included in the study; the primary presentation, documented risk factors, and postoperative pathological results were evaluated. Conclusion: The present study showed that risk of submandibular gland metastasis in clinically early-stage oral cavity squamous cell carcinoma was almost nil.

Integrated prediction and decision models are valuable in informing personalized decision making

ObjectivesTo show how prediction models can be incorporated into decision models, to allow for personalized decisions, and to assess the value of this approach using the management of the neck in early-stage oral cavity squamous cell carcinoma as an example. Study Design and SettingIn a decision model, three approaches were compared: a “population-based” approach in which patients undergo the strategy that is optimal for the population; a “perfectly predicted” approach, in which each patient receives the optimal strategy for that specific patient; and a “prediction model” approach in which each patient receives the strategy that is optimal based on prediction models. The average differences in costs and quality-adjusted life years (QALYs) for the population between these approaches were studied. ResultsThe population-based approach resulted on average in 4.9158 QALYs with €8,675 in costs, per patient. The perfectly predicted approach yielded 0.21 more QALYs and saved €1,024 per patient. The prediction model approach yielded 0.0014 more QALYs and saved €152 per patient compared with the population-based approach. ConclusionThe perfectly predicted approach shows that personalized care is worthwhile. However, current prediction models in the field of oral cavity squamous cell carcinoma have limited value. Incorporating prediction models into decision models appears to be a valuable method to assess the value of personalized decision making.