Early-stage Oral Squamous Cell Carcinoma Research Articles

MRI-based deep learning and radiomics for prediction of occult cervical lymph node metastasis and prognosis in early-stage oral and oropharyngeal squamous cell carcinoma: a diagnostic study.

The incidence of occult cervical lymph node metastases (OCLNM) is reported to be 20%-30% in early-stage oral cancer and oropharyngeal cancer. There is a lack of an accurate diagnostic method to predict occult lymph node metastasis and to help surgeons make precise treatment decisions. To construct and evaluate a preoperative diagnostic method to predict occult lymph node metastasis (OCLNM) in early-stage oral and oropharyngeal squamous cell carcinoma (OC and OP SCC) based on deep learning features (DLFs) and radiomics features. A total of 319 patients diagnosed with early-stage OC or OP SCC were retrospectively enrolled and divided into training, test and external validation sets. Traditional radiomics features and DLFs were extracted from their MRI images. The least absolute shrinkage and selection operator (LASSO) analysis was employed to identify the most valuable features. Prediction models for OCLNM were developed using radiomics features and DLFs. The effectiveness of the models and their clinical applicability were evaluated using the area under the curve (AUC), decision curve analysis (DCA) and survival analysis. Seventeen prediction models were constructed. The Resnet50 deep learning (DL) model based on the combination of radiomics and DL features achieves the optimal performance, with AUC values of 0.928 (95% CI: 0.881-0.975), 0.878 (95% CI: 0.766-0.990), 0.796 (95% CI: 0.666-0.927) and 0.834 (95% CI: 0.721-0.947) in the training, test, external validation set1 and external validation set2, respectively. Moreover, the Resnet50 model has great prediction value of prognosis in patients with early-stage OC and OP SCC. The proposed MRI-based Resnet50 deep learning model demonstrated high capability in diagnosis of OCLNM and prognosis prediction in the early-stage OC and OP SCC. The Resnet50 model could help refine the clinical diagnosis and treatment of the early-stage OC and OP SCC.

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.

Prognostic Factors for Locoregional Control in Early-Stage Oral Tongue Squamous Cell Carcinoma Treated with Partial Glossectomy and Elective Neck Dissection

Prognostic Factors for Locoregional Control in Early-Stage Oral Tongue Squamous Cell Carcinoma Treated with Partial Glossectomy and Elective Neck Dissection

Use of Indocyanine Green Near-Infrared Imaging for Sentinel Lymph Node Biopsy in Early Oral Squamous Cell Carcinoma: A Pilot Study

PurposeThe current established technique for sentinel lymph node (SLN) biopsy is preoperative injection of 99mtechnetium-labeled nanosized colloids (99mTc) followed by single photon emission computed tomography and standard computed tomography (SPECT/CT) with subsequent intraoperative gamma probe-guided excision of the SLN. It is however time and resource consuming, causes radiation exposure and morbidity for the patient as the injection is done in the awake patient. Recently near-infrared imaging with indocyanine green (ICG) gained importance in SLN biopsy as a faster and more convenient technique. The objective of our study was to investigate the feasibility of SLN biopsy using ICG-imaging in early oral squamous cell carcinoma (OSCC).MethodsSingle-centre pilot study of five patients with early-stage OSCC. For all patients, both techniques (99mTc and ICG) were performed. We injected 99mTc preoperatively in the awake patient, followed by SPECT/CT imaging. Intraoperatively ICG was injected around the primary tumor. Then the neck incision was performed according to the SPECT/CT images and SLN were detected by using a gamma probe and near-infrared fluorescence imaging of the ICG-marked lymph nodes intraoperatively. The excised lymph nodes were sent to histopathological examination according to the SLN dissection protocol.ResultsIn all five patients sentinel lymph nodes were identified. A total of 7 SLN were identified after injection of 99mTc, imaging with SPECT/CT and intraoperative use of a gamma probe. All these SLN were fluorescent and visible with the ICG technique. In two patients, we could identify additional lymph nodes using the ICG technique. Pathological analysis demonstrated occult metastasis in two of the cases.ConclusionsOur study shows that ICG-guided SLN biopsy is a feasible technique, especially in combination with conventional radioisotope method and may help for intraoperative localization of SLN. Validation studies with bigger patient cohorts are needed to prove our results.

Beta-defensin index: A functional biomarker for oral cancer detection

There is an unmet clinical need for a non-invasive and cost-effective test for oral squamous cell carcinoma (OSCC) that informs clinicians when a biopsy is warranted. Human beta-defensin 3 (hBD-3), an epithelial cell-derived anti-microbial peptide, is pro-tumorigenic and overexpressed in early-stage OSCC compared to hBD-2. We validate this expression dichotomy in carcinoma in situ and OSCC lesions using immunofluorescence microscopy and flow cytometry. The proportion of hBD-3/hBD-2 levels in non-invasively collected lesional cells compared to contralateral normal cells, obtained by ELISA, generates the beta-defensin index (BDI). Proof-of-principle and blinded discovery studies demonstrate that BDI discriminates OSCC from benign lesions. A multi-center validation study shows sensitivity and specificity values of 98.2% (95% confidence interval [CI] 90.3-99.9) and 82.6% (95% CI 68.6-92.2), respectively. A proof-of-principle study shows that BDI is adaptable to a point-of-care assay using microfluidics. We propose that BDI may fulfill a major unmet need in low-socioeconomic countries where pathology services are lacking.

Margin to depth of invasion ratio as an indicator for stratifying close margins in early-stage oral squamous cell carcinoma

ObjectivesIn early-stage oral squamous cell carcinoma (OSCC) patients, whether the margin-to-depth-of-invasion ratio (MDR) can assist in stratifying the prognosis remains unclear. MethodsPatients diagnosed with early stage OSCC at National Taiwan University Hospital between January 2007 and December 2021 were reviewed. Patients with margin > 1 mm were classified into two groups: MDR < 0.5 and MDR ≥ 0.5. ResultsWe analyzed 911 pT1-2N0M0 OSCC patients, 723 (79.36 %) with MDR ≥ 0.5 and 188 (20.64 %) with MDR < 0.5. Patients in the MDR < 0.5 group displayed a significantly higher local recurrence rate (odds ratio 2.81, p = 0.002) compared with MDR ≥ 0.5 group. The 5-year disease-free survival were 80.8 % for clear margin, 76.3 % for close margin (MDR ≥ 0.5), and 65.2 % for close margin (MDR < 0.5). The overall survival displayed a similar pattern, with 5-year rates of 88.3 % for clear margin, 86.8 % for close margin (MDR ≥ 0.5), and 75.0 % for close margin (MDR < 0.5). There were no significant overall survival differences between the two MDR ≥ 0.5 groups, but both were significantly superior to patients with MDR < 0.5 (p = 0.001; p = 0.01). After multivariant cox analysis, MDR < 0.5 was a significant risk factor for disease-free survival (p < 0.001). ConclusionFor early stage OSCC patients without positive margin (≦1mm), the survival outcome between MDR ≥ 0.5 group and MDR < 0.5 group was significantly different. The MDR < 0.5 group had significantly higher risk of local recurrence that may warrant adjuvant treatment.

The prognostic role of single cell invasion and nuclear diameter in early oral tongue squamous cell carcinoma

BackgroundThe clinical significance of single cell invasion and large nuclear diameter is not well documented in early-stage oral tongue squamous cell carcinoma (OTSCC).MethodsWe used hematoxylin and eosin-stained sections to evaluate the presence of single cell invasion and large nuclei in a multicenter cohort of 311 cases treated for early-stage OTSCC.ResultsSingle cell invasion was associated in multivariable analysis with poor disease-specific survival (DSS) with a hazard ratio (HR) of 2.089 (95% CI 1.224–3.566, P = 0.007), as well as with disease-free survival (DFS) with a HR of 1.666 (95% CI 1.080–2.571, P = 0.021). Furthermore, large nuclei were associated with worse DSS (HR 2.070, 95% CI 1.216–3.523, P = 0.007) and with DFS in multivariable analysis (HR 1.645, 95% CI 1.067–2.538, P = 0.024).ConclusionSingle cell invasion and large nuclei can be utilized for classifying early OTSCC into risk groups.

Identification of saliva biomarkers as tools for detection of early-stage oral squamous cell carcinoma

Cancer of the flat squamous cells of the oral cavity is called Oral Squamous Cancer Cell (OSCC). OSCC is responsible for 95% of all oral cancers. In high-risk countries like Pakistan, OSCC has one of the highest mortality rates amongst the general demographic. With most OSCC cases being identified in later stages, the 5-year survival rates have remained as low as 50%. However, with early diagnosis, OSCC patients have been shown to have a better chance of surviving. To that effect, identifying potential biomarkers to act as diagnostic indicators for OSCC can help in early diagnosis of the disease. An emerging field for alternative detection of cancer are non-invasive methods that use saliva as a fluid for liquid biopsies. Saliva comprises proteomes, microbiomes, metabolomes, transcriptomes, and genomes that can be used as potential tools for the early detection of cancer. “Salivaomics” has established itself as a promising area for diagnostic and prognostic purposes. In this review paper, we perform a meta-analysis and a systematic literature review to catalogue biomarkers found in saliva that could potentially be used in the early diagnosis of OSCC.

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.

Controversies in the treatment of early-stage oral squamous cell carcinoma

The treatment of early-stage oral squamous cell carcinoma (OSCC) is still a controversial issue. Thanks to the 8th edition of TNM by AJCC there is a better distinction between the stages of OSCC. However, Stages I and II still share the same treatment protocol, even if the prognosis is radically different. A retrospective study has been conducted including 70 previously untreated patients with Stage I or II OSCC, treated with tumorectomy and selective neck dissection. The study focuses on the link between pT1/2 and various other factors, particularly histological grading, vascular and perineural invasion, local and cervical recurrence, surgical margins and overall survival. These data reveal significant differences between pT1 and pT2 in histological grade, perineural invasion, cervical recurrence, surgical margins, and overall survival, emphasizing the necessity of different treatment protocols for T1 and T2 OSCC. Distinct strategies should be proposed to treat Stage I and II OSCC, with Stage II patients possibly benefitting from more aggressive treatments: following these data, a wait-and-see strategy should only be considered in Stage I, while certain treatments at the cervical level — such as prophylactic neck dissection and sentinel node biopsy — should always be considered for Stage II tumors.

Prognostic study of sentinel lymph node biopsy in early-stage oral squamous cell carcinoma with computed tomography lymphography

PurposeOccult metastasis is a prognostic factor for early-stage oral squamous cell carcinoma (OSCC). Sentinel lymph node (SLN) biopsy (SLNB) is a promising method to detect such metastases. The present study aimed to evaluate the diagnostic reliability of SLNB with computed tomography lymphography (CTL) for early-stage OSCC and to clarify patient outcomes after SLNB. MethodsThe medical records of 42 patients with T1 or T2 cN0 OSCC who had undergone CTL the day before surgery were retrospectively collected and statistically analyzed. ResultsSLNs were identified on CTL in 41 of 42 OSCC patients (97.6 %). Micrometastases were detected in 10 of 41 cases (24.4 %) and 11 of 65 SLNs (16.9 %) by intraoperative pathological diagnosis. Three cases showed occult metastasis within a year after the primary operation. Specificity and negative predictive value were 76.9 % and 90.3 %, respectively. The cumulative 5-year regional recurrence-free rate was 89.7 % in 31 SLNB-negative patients. Five-year overall and disease-free survival rates were 86.9 % and 70.1 %, respectively, in the 41 cases with identified SLNs. ConclusionCTL offers acceptable results and appears likely to be effective in treating early-stage OSCC patients with low-invasive surgery. Further investigation is necessary to compare radioisotope-based methods.

Nivolumab for Patients With High-Risk Oral Leukoplakia

Proliferative verrucous leukoplakia (PVL) is an aggressive oral precancerous disease characterized by a high risk of transformation to invasive oral squamous cell carcinoma (OSCC), and no therapies have been shown to affect its natural history. A recent study of the PVL immune landscape revealed a cytotoxic T-cell-rich microenvironment, providing strong rationale to investigate immune checkpoint therapy. To determine the safety and clinical activity of anti-programmed cell death 1 protein (PD-1) therapy to treat high-risk PVL. This nonrandomized, open-label, phase 2 clinical trial was conducted from January 2019 to December 2021 at a single academic medical center; median (range) follow-up was 21.1 (5.4-43.6) months. Participants were a population-based sample of patients with PVL (multifocal, contiguous, or a single lesion ≥4 cm with any degree of dysplasia). Patients underwent pretreatment biopsy (1-3 sites) and then received 4 doses of nivolumab (480 mg intravenously) every 28 days, followed by rebiopsy and intraoral photographs at each visit. The primary end point was the change in composite score (size and degree of dysplasia) from before to after treatment (major response [MR]: >80% decrease in score; partial response: 40%-80% decrease). Secondary analyses included immune-related adverse events, cancer-free survival (CFS), PD-1 ligand 1 (PD-L1) expression, 9p21.3 deletion, and other exploratory immunologic and genomic associations of response. A total of 33 patients were enrolled (median [range] age, 63 [32-80] years; 18 [55%] were female), including 8 (24%) with previously resected early-stage OSCC. Twelve patients (36%) (95% CI, 20.4%-54.8%) had a response by composite score (3 MRs [9%]), 4 had progressive disease (>10% composite score increase, or cancer). Nine patients (27%) developed OSCC during the trial, with a 2-year CFS of 73% (95% CI, 53%-86%). Two patients (6%) discontinued because of toxic effects; 7 (21%) experienced grade 3 to 4 immune-related adverse events. PD-L1 combined positive scores were not associated with response or CFS. Of 20 whole-exome sequenced patients, all 6 patients who had progression to OSCC after nivolumab treatment exhibited 9p21.3 somatic copy-number loss on pretreatment biopsy, while only 4 of the 14 patients (29%) who did not develop OSCC had 9p21.3 loss. This immune checkpoint therapy precancer nonrandomized clinical trial met its prespecified response end point, suggesting potential clinical activity for nivolumab in high-risk PVL. Findings identified immunogenomic associations to inform future trials in this precancerous disease with unmet medical need that has been difficult to study. ClinicalTrials.gov Identifier: NCT03692325.

Salivary Interleukin-1 Levels in Oral Squamous Cell Carcinoma: A Case-Control Study.

Oral squamous cell carcinoma (OSCC) is a prevalent malignancy with a significant impact on global health. The identification of non-invasive biomarkers for early detection and monitoring of OSCC remains crucial. A total of 100 subjects, comprising 50 patients with histopathologically confirmed OSCC and 50 age- and sex-matched healthy controls, were enrolled in the study. Salivary samples were collected from all participants and analyzed using enzyme-linked immunosorbent assays (ELISA) to measure IL-1 levels. Clinical data, including demographic information, smoking habits, and alcohol consumption, were obtained from patient records. The mean salivary IL-1 level was significantly higher in OSCC patients compared to healthy controls (P < 0.001). Furthermore, subgroup analysis demonstrated that advanced stages of OSCC correlated with significantly elevated IL-1 levels when compared to early-stage OSCC (P < 0.05). Additionally, high salivary IL-1 levels were associated with a more aggressive tumor phenotype and poorer prognosis, as reflected by tumor size, lymph node metastasis, and overall survival (P < 0.01). This case-control study provides compelling evidence that salivary Interleukin-1 (IL-1) levels are significantly elevated in patients with OSCC.

Evaluation of micrometastasis and isolated tumor cells in node-negative early-stage oral tongue squamous cell carcinoma: a cross-sectional study in tertiary-level hospitals in eastern India

The present study aimed to investigate the incidence of micrometastasis (MMs) and isolated tumor cells (ITCs) in node-negative early-stage oral tongue squamous cell carcinoma (T1-T2 N0). The secondary objective was to correlate the incidence with the clinicopathologic parameters of age, sex, depth of invasion, pattern of invasion, host lymphocytic response, and size and grade of primary tumor. Micrometastasis and ITCs in cervical nodes of 30 patients with early-stage oral tongue squamous cell carcinoma were detected and compared using 3 methods: routine hematoxylin and eosin staining, serial-sectioning at intervals of 150 microns employing hematoxylin and eosin, and serial sectioning pan-cytokeratin immunostaining. Associations with clinicopathological variables were analyzed. Metastatic tumor cells were detected in the cervical nodes of 2 patients using serial sectioning and immunohistochemistry, resulting in upstaging of 6.6% of all cases. Level I and II lymph nodes were primarily involved. Early-stage oral tongue squamous cell carcinoma has a significant potential for MMs that frequently go undetected in routine histopathologic examination. However, laborious and technique-sensitive, serial sectioning in combination with pan-cytokeratin staining (AE1/AE3) may aid in detecting MMs and ITCs in patients with early-stage OTSCC.

Radioactive nanosized colloids and indocyanine green identify the same sentinel lymph nodes in oral squamous cell carcinoma

PurposeNear-infrared fluorescence imaging using indocyanine green (ICG) combined with radioactive markers has the potential to improve sentinel lymph-node (SLN) mapping in oral squamous cell carcinoma (OSCC). This study aimed to evaluate the ability of 99mTc and ICG in identifying the sentinel lymph nodes in patients with early stage OSCC.MethodsData were collected prospectively, and a retrospective analysis of 15 patients with early stage OSCC and a cN0 neck was performed. All patients received peritumoral injection of 99mTc the day before surgery and ICG was administered intraoperatively. Intentionally, the application of the two different tracers were done by two different physicians with varying degrees of experience. The number of identified lymph nodes positive for 99mTc and ICG, the overlap or possible discrepancies of both methods, and the time until fluorescence signals of ICG were detected were noted.ResultsIn all patients, a 100% agreement in sentinel lymph-node identification was achieved, regardless of both the exact location of the peritumoral injection and the experience of the injecting surgeon. Time until ICG accumulation in the sentinel lymph node was consistently found to be between 1 and 3 min.ConclusionICG constitutes a viable and useful addition to 99mTc for intraoperative sentinel lymph-node detection in this study.

Evaluation of neck control strategies for oral squamous cell carcinoma of stage I: Neck dissection or potential immunotherapy

The neck control strategies of early-stage oral squamous cell carcinoma (OSCC) patients with clinical node-negative neck remain uncertain. These patients could be benefit from elective neck dissection (END) alongside primary tumor excision; but current evidence on END versus observation for OSCC of stage I only is not yet analyzed collectively in detail. Herein, this short communication aimed to evaluate the neck control strategies of stage I OSCC, mainly END versus observation. A total of 740 patients with stage I OSCC, comprising 434 underwent END and 306 received observation, were identified from literature. The results showed that stage I OSCC patients would not be benefit from END based on the analysis of neck nodal recurrence and overall survival. An ideal strategy would likely be to avoid neck dissection for stage I OSCC patients with N0 neck. Immune checkpoint therapy is such a potential strategy, which aims at eliciting potent antitumor immune responses within lymph nodes hold promise for treating patients with early-stage OSCC and may prove more efficacious than lymphadenectomy in a variety of scenarios. Consequently, neck dissection for stage I OSCC could be approached with caution, particularly in patients receiving immune checkpoint therapy.

High-sensitive and rapid electrochemical detection of miRNA-31 in saliva using Cas12a-based 3D nano-harvester with improved trans-cleavage efficiency

Salivary miRNA-31 is a reliable diagnostic marker for early-stage oral squamous cell carcinoma (OSCC), but accurate detection of miRNA-31 in saliva samples is a challenge because of its low level and high sequence homology. The CRISPR/Cas12a system has the exceptional potential to enable simple nucleic acid analysis but suffers from low speed and sensitivity. To achieve rapid and high-sensitive detection of miRNA-31 using the CRISPR/Cas12a system, a Cas12a-based nano-harvester activated by a polymerase-driven DNA walker, named as dual 3D nanorobots, was developed. The target walked rapidly on the surface of DNA hairpin-modified magnetic nanoparticles driven by DNA polymerase, generating numerous double-strand DNA (dsDNA). Then, the Cas12a bound to the generated dsDNA for activating its trans-cleavage activity, forming 3D nano-harvester. Subsequently, the harvester cut and released methylene blue-labeled DNA hairpins immobilized on the sensing interface, leading to the change in electrochemical signal. We found that the trans-cleavage activity of the harvester was higher than the conventional CRISPR/Cas12a system. The developed dual 3D nanorobots could enable rapid (detection time within 60 min), high-sensitive (detection limit of femtomolar), and specific analysis of miRNA-31 in saliva samples. Thus, our established electrochemical biosensing strategy has great potential for early diagnosis of OSCC.

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.

Free-Flap Reconstruction in Early-Stage Squamous Cell Carcinoma of the Oral Cavity-A Prospective Monocentric Trial to Evaluate Oncological Outcome and Quality of Life.

Surgery is generally accepted as standard treatment in oral cancer, but the reconstructive procedures remain a matter of debate. The aim of this study was to evaluate oncological outcome and quality of life following surgical resection and free-flap reconstruction in patients with early oral squamous cell carcinoma. The presented trial was performed as a prospective, single-center observation study. Inclusion criteria were primary surgery in early-stage oral squamous cell carcinoma with free-flap reconstruction. Endpoints were overall and progression-free survival and quality of life up to 24 months after surgery. Twenty-six patients were included. Overall survival was 100% and progression-free survival was 92.3% in a maximum follow-up time of 21 months. Global quality of life showed no significant alteration after surgery. Patients reported a significant reduction in pain (p = 0.048) and a decreasing impairment of speech one year after surgery (p = 0.021). Free-flap reconstruction is a safe procedure that results in excellent oncological outcome and quality of life. Functional outcome is of high relevance in early-stage tumors of the head and neck and may mostly be affected by reconstructive procedures. Therefore, a prospective evaluation to explore success and the effects of surgical therapy is highly warranted.

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.