Cavity Squamous Cell Carcinoma Patients Research Articles

Abstract C028: Decreased heterogeneity in immune interactions in oral cavity squamous cell carcinoma patients with recurrence

Abstract There have been improvements in clinical risk stratifications for oral cavity squamous cell carcinoma (OSCC) with the AJCC 8th edition staging system. Other studies suggest the addition of a metric of specific immune interactions in and around the tumor may be helpful to further stratify patients, with mixed findings. The advent of spatial imaging has allowed a global view for assessing tumor features in the context of all surrounding cell interactions. We hypothesize that the lack of architectural information could contribute to varied clinical outcomes in previous studies, such as tumor recurrence. This highlights how spatial technologies could aid in understanding the role of tissue architecture and its influence on biology and medicine. To study tissue remodeling spatially, we focused on multiplexed-ion beam imaging (MIBI), a spatial proteomics platform to visualize 40 immuno-onco proteins simultaneously. Our banked patient cohort consists of 20 recurrent and 49 non-recurrent OSCC primary surgery samples. Clinical metadata capturing pathologic stage, alcohol use, smoking history, survival data, and more were also collected. With our pathologist, we curated 290 field-of-views (FOVs) of matched primary tumors, uninvolved lymph nodes, and metastatic lymph nodes (if any). Downstream computational analysis using existing MIBI codebases augmented with in-house spatial analytics has revealed a robust spatial dataset. After using machine-learning algorithms to cell segment our images, we validated these assigned cells and marker staining to further annotate cell populations. When we analyzed direct cell interactions, there was a decrease in heterogeneity in immune interactions within recurrent patients compared to non-recurrent patients. To ascertain how the loss of these interactions affected recurrence prognosis, we investigated their prevalence within the tumor border vicinity. We hypothesize that the proximity and cell-cell interactions near the border will promote a tumor-suppressive environment. Utilizing centroid-to-centroid distance measurements, we distilled the top 30 cell-cell interactions within a 100-micron distance from the tumor border. Cell pairs involving macrophage tissue-resident memory cells and CD8 T memory resident cells were more abundant in recurrent patients, while pairs involving CD4 T regulatory and CD8 cells were found in non-recurrent patients. Reassuringly, cell pairings involving myeloid cells were upregulated in the recurrent cohort as expected. Interestingly, cancer-associated fibroblast cell pairings were upregulated indiscriminately in both patient sub- cohorts. This suggests that the impact of certain known immunosuppressive changes may contribute in varying amounts to disease control. Our data demonstrates differences in the architecture of tumors with known divergent outcomes, which suggests global tissue-level changes could be a predictive factor. Clinically, interrogating these interactions of interest could guide treatment escalation or de-escalation in the future. Citation Format: Connie J. Zhou, Jane Lee, Rebecca Jaszczak, Steven R. Long, Patrick K. Ha, Matthew H. Spitzer. Decreased heterogeneity in immune interactions in oral cavity squamous cell carcinoma patients with recurrence [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr C028.

917P Automatic characterization of spatial arrangement of tumor-infiltrating lymphocytes identifies oral cavity squamous cell carcinoma patients with poorer prognosis

917P Automatic characterization of spatial arrangement of tumor-infiltrating lymphocytes identifies oral cavity squamous cell carcinoma patients with poorer prognosis

Socioeconomic Status, Length of Stay, and Postoperative Complications in Oral Cavity Squamous Cell Carcinoma.

Background: Despite universal healthcare in Canada, low socioeconomic status (SES) has been associated with worse survival in oral cavity squamous cell carcinoma (OCSCC) patients. However, the relationship between SES and outcomes during the acute postoperative period is poorly defined. Hamilton, Ontario, presents a unique population with widely varying SES within the same geography. The objective of this study was to examine the relationship between SES, length of hospital stay (LOHS), and postoperative complications in OCSCC. Methods: Newly diagnosed OCSCC patients receiving primary surgical treatment from 2010 to 2014 were identified within a prospectively collected database. Inclusion criteria included age >18 years old, pathological diagnosis of oral cavity cancer, and primary surgical treatment with curative intent. Patients were excluded if they were undergoing palliative treatment or had previous head and neck surgery/radiotherapy. Postal codes were used to identify neighborhood-level socioeconomic variables via 2011 Canada Census data. Income quartiles were defined from groups of neighboring municipalities based on Canada Census definitions. Demographic, social, pathological, staging, and treatment data were collected through chart review. Results: One hundred and seventy-four patients were included in the final analysis. OCSCC patients with lower SES were more likely to be younger (P = .041), male (P = .040), have significant tobacco and alcohol use (P = .001), higher Charlson Comorbidity Index (CCI; P = .014), lower levels of education (P = .001), and have lower employment levels (P = .001). Lower SES patients had higher clinical tumor (P = .006) and clinical nodal (P = .004) staging and were more likely to receive adjuvant therapy (P = .001) and G-tubes (P = .001). Multivariable regression analysis showed that low SES was a statistically significant predictor of postoperative complications [β 2.50 (95% confidence interval (CI) 0.200, 3.17); P = .014] and LOHS [β 2.03 (95% CI 1.06, 2.99); P = .0001]. Tobacco and alcohol use, clinical tumor, and nodal stage, CCI, and planned adjuvant therapy were also statistically significant predictors of postoperative complications and LOHS (P < .05). Conclusion: Patients with lower SES have more advanced OCSCC disease with increased comorbidities that owes itself to more acute postoperative complications and LOHS within this study population. Patients with low SES should be identified as patients that require more support during their cancer treatment.

Efficacy and safety of induction chemotherapy in oral cavity cancer: An eight-year experience at a Portuguese reference center.

Induction chemotherapy has been described as an option in locally advanced oral cavity squamous cell carcinoma when the surgical morbidity is expected to be high. This work aimed to evaluate the outcome and safety of induction chemotherapy in this setting. We performed a retrospective and observational study including patients with oral cavity squamous cell carcinoma, treated with induction chemotherapy between January 2010 and December 2018. Outcomes included induction chemotherapy toxicity, treatment response, disease-free survival and overall survival. A total of 108 oral cavity squamous cell carcinoma patients were included. Ninety-six (88.9%) had stage IV disease, while 12 (11.1%) had stage III. Eighty-four patients (80.8%) achieved at least a partial response to induction chemotherapy at clinical evaluation, and 75 (72.1%) at radiological evaluation. Seventy-eight patients have been proposed for subsequent definitive treatments, with no differences obtained in prognosis, when comparing surgical to non-surgical approaches. In patients treated with definitive treatments, improved five-year disease-free survival was obtained if at least a clinical (56.3%; p=0.001) or radiological (52.9%; p=0.001) partial response was achieved after induction chemotherapy. Similarly, superior five-year overall survival was verified for those achieving at least clinical (51.1%; p<0.0001) or radiological (52.6%; p=0.001) partial response. Also, accomplishing a pathologic complete response (n=22.6%) significantly improved disease-free survival (p=0.039) and overall survival (p=0.005). Grade 3 and 4 toxicities were observed in 52 patients (41.8%). Responses to induction chemotherapy predicted prognosis in our population, however important toxicities were observed. Further studies are necessary to identify induction chemotherapy response predictors and subgroups who may benefit from this approach.

Radiomic biomarkers of locoregional recurrence: prognostic insights from oral cavity squamous cell carcinoma preoperative CT scans.

This study aimed to identify CT-based imaging biomarkers for locoregional recurrence (LR) in Oral Cavity Squamous Cell Carcinoma (OSCC) patients. Computed tomography scans were collected from 78 patients with OSCC who underwent surgical treatment at a single medical center. We extracted 1,092 radiomic features from gross tumor volume in each patient's pre-treatment CT. Clinical characteristics were also obtained, including race, sex, age, tobacco and alcohol use, tumor staging, and treatment modality. A feature selection algorithm was used to eliminate the most redundant features, followed by a selection of the best subset of the Logistic regression model (LRM). The best LRM model was determined based on the best prediction accuracy in terms of the area under Receiver operating characteristic curve. Finally, significant radiomic features in the final LRM model were identified as imaging biomarkers. Two radiomics biomarkers, Large Dependence Emphasis (LDE) of the Gray Level Dependence Matrix (GLDM) and Long Run Emphasis (LRE) of the Gray Level Run Length Matrix (GLRLM) of the 3D Laplacian of Gaussian (LoG σ=3), have demonstrated the capability to preoperatively distinguish patients with and without LR, exhibiting exceptional testing specificity (1.00) and sensitivity (0.82). The group with LRE > 2.99 showed a 3-year recurrence-free survival rate of 0.81, in contrast to 0.49 for the group with LRE ≤ 2.99. Similarly, the group with LDE > 120 showed a rate of 0.82, compared to 0.49 for the group with LDE ≤ 120. These biomarkers broaden our understanding of using radiomics to predict OSCC progression, enabling personalized treatment plans to enhance patient survival.

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.

Oral Cavity Squamous Cell Carcinoma: Impact of Clear Margin Distance on Locoregional Control in Patients Undergoing Postoperative Radiotherapy.

Postoperative radiotherapy can improve locoregional control (LC) in oral cavity squamous cell carcinoma (OCSCC) patients with positive resection margins. The present study aimed to evaluate the impact of surgical margin size on LC in this patient population. This retrospective study involved 162 patients with OCSCC who underwent postoperative radiotherapy between 2000 and 2020 at the Department of Radiation Oncology, University Hospital Heidelberg and the German Cancer Research Center. The study aimed to determine the impact of different resection margins on LC, as well as overall survival (OS), progression-free survival (PFS), and treatment-related toxicity (CTCAE 4.03). Seventy-seven patients (47.5%) had involved (<1 mm) margins, 22 patients (13.6%) close (≤5 mm) margins, and 63 patients (38.9%) clear (>5 mm) margins. A surgical margin ≤ 5 mm was a significant predictor for worse LC (HR 2.6, 95% CI 1.2, 6.1), but not for OS (HR 1.2, CI 0.7, 1.9) or PFS (HR 1.2, 0.7, 2.0). Patients who have narrow resection margins (1-5 mm) experience poor local control and should receive postoperative radiotherapy. It is necessary to conduct further prospective studies to determine whether a narrower margin window could be achieved to better determine the appropriate indication for adjuvant radiotherapy.

The Oncological Safety of Submental Flap Reconstruction in Head-and-Neck Cancers: An Extended Follow-up Study.

The oncological safety of a submental (SM) flap is thought to be controversial. The objective of our study was to validate our previous study regarding the oncological safety of SM flaps in oral cavity reconstruction. An electronic database was searched from 2015 to 2021 for all head-and-neck tumor patients, where reconstruction was performed using a SM flap. Eighty-eight oral cavity squamous cell carcinoma patients, among whom 71 were males (81.8%), with a mean age of 55.3 years (range: 25-79 years), were retrieved from the database. The sites of involvement were 37 buccal mucosa, 27 lower alveolus, and 24 tongues. The mean follow-up was 33.5 months. The SM flap reconstruction was done for 88 patients; 3 had complete loss of flap, 17 had incomplete loss/partial necrosis, and 68 patients had uneventful recovery of the flap. We had 16 patients with local recurrence. Of these, 4 (4.5%) patients had clear margins and no lymphadenopathy at the level I at the final histopathology report. This study provides validation of the oncological safety of the SM flap and establishes that nodal positivity at level I alone does not contribute to recurrence at the primary site.

Clinical outcomes and impact of prognostic factors in resectable oral cavity squamous cell carcinoma.

To evaluate clinical outcomes and prognostic factors in non-metastatic oral cavity squamous cell carcinoma (OCSCC) patients who underwent surgery with or without adjuvant therapy. From 2007 and 2018, 116 patients were analyzed. The primary endpoint was overall survival (OS), and secondary endpoints were disease-free survival (DFS), local failure (LF), regional failure (RF), and distant metastases (DM). Kaplan-Meier method and log-rank test assessed survival outcomes, while Cox proportional hazard tests analyzed prognostic factors. Median patient age was 53 years, most were smokers (93.5%) and males (62.9%). Predominant subsite was the oral tongue (58.6%). Treatment included surgery alone (16.4%), adjuvant radiotherapy (46.6%), or adjuvant concurrent chemoradiotherapy (CCRT) (37%). The median follow-up time was 45.9 months. There were significant differences between groups in terms of gender (P=0.028) and RT dose (P=0.01). The 3-year OS, DFS, LF, RF and DM for the entire cohort were 60.9%, 55.1%, 20.11%, 8.43%, and 17.13%, respectively. Surgery alone yielded higher 3-year OS (81.4%) than adjuvant RT (70%) or adjuvant CCRT (41.4%), (p=0.012). Adjuvant CCRT correlated with higher LF compared to adjuvant RT and surgery alone groups (p=0.029). Lymphovascular invasion (LVI) impacted OS (HR=2.034, p=0.0498) and DM (HR=3.380, p=0.0132), while higher tumor grade increased DM likelihood (HR=8.477, p=0.0379). This study reports OCSCC patient outcomes in Jordan across different treatment modalities. Adjuvant CCRT correlated with higher LF rates, and LVI impacted OS and DM, aligning with existing OCSCC treatment literature.

Oral Cavity Squamous Cell Carcinomas in Patients with a History of Oral Lichen Planus: Frequency and Outcomes

Oral lichen planus (OLP) is an inflammatory condition which affects the mucous membranes of the oral cavity. While previous studies have described the association between OLP and development of oral cavity cancer, there is currently a paucity of literature examining the impact of this disease on treatment response and prognosis. As such, we present a retrospective cohort study of Oral cavity squamous cell carcinoma (OCSCC) patients with a history of OLP to explore the course of their disease. Using an IRB approved tertiary care registry of head and neck cancer patients, we identified patients with OCSCC who had a prior diagnosis of OLP. The number of new primary tumors, rates of local (LF), regional (RF) and distant failure (DF), as well as overall survival (OS) were assessed using Cox proportional hazards and Kaplan Meier analysis for actuarial survival estimates. Fifty-four patients with OCSCC and OLP were identified with 109 individual OCSCC diagnoses. Patients had a median age of 67 years, were predominantly female (n = 42, 77.8%) and never smokers (n = 29, 53.7%) with a median follow up after diagnosis of OCSCC of 46.5 months. Nine patients (16.7%) had a history of immunosuppression of whom 6 (11.1%) had chronic steroid use for treatment of OLP. Within the cohort, 33 (61.1%) of OLP patients had a single OCSCC, 11 (20.4%) had 2, and 10 (18.5%) had >3 separate tumors develop. The most common oral cavity subsites were oral tongue (n = 42, 38.5%), followed by alveolar ridge (n = 14, 12.8%) and gingiva (n = 13, 11.9%). Papillary SCC subtype was identified in 10.1%. 92.7% of tumors (n = 101) were treated with primary surgery, with 23 (21.1%) receiving adjuvant RT and 10 of those patients receiving concurrent chemotherapy. Among resected patients, pathologic stages were predominantly T1-2 (84.1%) and N0 (50% vs N1 15.6% and N2a-3 34.4%). The mean RT dose was 62 Gy in 32 fractions. Locoregional failure occurred in 24.8% of cancers (n = 27), with local and regional failure occurring in 13.8% (n = 15) and 11% (n = 12) of lesions, respectively. Recurrence free survival at 3 and 5 years was 75% and 70.3%, respectively, with overall survival at 3 and 5 years of 71.1% and 67%, respectively. Patients with OCSCC and a history of OLP are predominantly female and never smokers. The tumors that develop in such patients are often early stage but a proportion of patients appear to be at higher risk of developing multiple malignancies and surveillance of this patient population to identify new tumors is crucial.

Small tumor invasion of metastatic lymph node can develop extranodal extension in oral cancer

ObjectiveExtranodal extension (ENE) of lymph node metastasis in oral cancer has been well demonstrated to reflect tumor aggressiveness. However, there are few studies to show the association between ENE and tumor invasion status of metastatic lymph node. The purpose of this study is therefore to investigate pathological nodal factors including tumor invasion status of ENE-positive lymph node and its association with clinical outcomes in oral cavity squamous cell carcinoma (OSCC) patients. MethodsWe identified OSCC patients with at least one pathologically ENE-positive node and measured area of metastasis within lymph node (inside metastasis), and area of metastatic lymph node. We defined tumor invasion ratio (TIR) as the ratio of inside metastasis area to metastatic lymph node area. ResultsWe observed that the value of TIR had a wide variation and that metastatic lymph nodes with small TIR can develop ENE. In addition, we demonstrated that tumors with smaller TIR had significantly worse DFS (HR 3.94, [1.21–12.83]; p = 0.014), OS (HR 5.38, [1.45–19.93]; p = 0.005), and more DM (HR 10.01, [1.17–86.0]; p = 0.001) than those with larger TIR. ConclusionThis is the first study to evaluate the detailed tumor invasion status of lymph node with ENE and showed that smaller TIR can develop ENE which was associated with clinical outcomes.

Real-Time Intraoperative Detection of Margins for Oral Cavity Squamous Cell Carcinoma.

Obtaining negative surgical cancer margins is the strongest predictor for the long-term survival of oral cavity squamous cell carcinoma patients. To verify that the tumor has been completely removed, surgeons rely on pathologic evaluation of frozen sections to determine surgical margins, which can be time-consuming and subjective. Herein, we detail the real-time intraoperative use of dynamic optical contrast imaging (DOCI), a novel imaging modality that rapidly distinguishes head and neck cancer from healthy adjacent tissues based on fluorescence decay information from spectral bands in the UV-VIS range. Analysis of DOCI revealed microscopic characterization sufficient for tissue type identification consistent with histology (p < .05). DOCI delivers a clinically relevant tool that may better inform and drive precision surgery, directly impacting surgical outcomes and improving overall survival for our patients.

Prophylactic versus reactive feeding approach in patients undergoing adjuvant radiation therapy for oral cavity squamous cell carcinoma: A propensity score matched-pair analysis.

To assess the efficacy of prophylactic versus reactive feeding strategy in oral cavity squamous cell carcinoma (OCSCC) patients receiving adjuvant radiation therapy (RT). This was a post hoc analysis of patients of OCSCC enrolled in a randomized trial comparing three adjuvant strategies. In this trial, till 2010, a prophylactic feeding approach was followed for all patients. Since January 2011, a reactive feeding approach was followed. Two hundred and sixty-eight in each cohort (total n= 526) were eligible for analysis after propensity score matching. At 6 weeks post-RT completion, the median weight loss in the prophylactic versus reactive cohort was 5 versus 3 kg, p= 0.002. At all other time points until 1 year, the median weight loss was lesser in reactive than in the prophylactic cohort. A reactive feeding tube approach should be preferred for OCSCC receiving adjuvant RT.

Comparison of surgical complications after curative surgery in patients with oral cavity squamous cell carcinoma and sarcopenia.

The study aims to clarify the association of sarcopenia with perioperative and postoperative complications in oral cavity squamous cell carcinoma (OCSCC) patients undergoing curative surgery and to understand the reasons causing the poor oncologic outcomes for OCSCC. We conducted a propensity score matching study to investigate the association of perioperative and postoperative outcomes in OCSCC patients with sarcopenia and without sarcopenia. A retrospective analysis of a large national data set from the Taiwan Cancer Registry Database was conducted. At least two claims for patients with a principal diagnosis of sarcopenia within the 12-month preoperative period were defined as the criteria for sarcopenia diagnosis (ICD-10-CM code M62.84). Sarcopenia was diagnosed through the measurement of low muscle strength and low muscle mass by any one of the patient's attending orthopaedic physician, rehabilitation physician, family medicine specialist or geriatrician. A multivariate logistic regression model was used to calculate the perioperative, and postoperative major complications. Our final cohort included 16293 patients with OCSCC (10862 and 5431 in the sarcopenia and nonsarcopenia groups, respectively) who were eligible for further analysis. The sarcopenia group was 10.40% female and 89.60% male, and the nonsarcopenia group was 9.74% female and 90.26% male. The mean age±standard deviation (SD) were 56.44±11.14 and 56.22±11.29 for sarcopenia and nonsarcopenia groups. OCSCC patients with sarcopenia undergoing curative surgery had a significantly higher blood transfusion rate and volume; longer intensive care unit (ICU) stay, and hospital stay; higher postoperative 30-day mortality (adjusted odds ratio [aOR]: 1.12, 95% confidence interval [CI] [1.07, 1.56]) and rates of pneumonia (aOR: 1.34, 95% CI [1.20, 1.50]), acute renal failure (aOR: 1.45, 95% CI [1.12, 1.87]) and septicaemia (aOR: 1.29, 95% CI [1.15, 1.45]); higher postoperative first-year mortality (aOR: 1.18, 95% CI [1.13, 1.51]) and rates of pneumonia (aOR: 1.43, 95% CI [1.30, 1.56]), acute myocardial infarction (aOR: 1.52, 95% CI [1.06, 2.18]) and septicaemia (aOR: 1.29, 95% CI [1.15, 1.45]). OCSCC patients with sarcopenia might exhibit more perioperative and surgical complications than those without sarcopenia.

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.

Comparison of sentinel lymph node biopsy and elective neck dissection for early oral cavity squamous cell carcinoma patients with clinically node-negative necks: systematic review and meta-analysis.

This study aimed to compare the prognostic utility of sentinel node biopsy and elective neck dissection in early stage clinically node-negative oral cavity squamous cell carcinoma patients. PubMed, Scopus, Embase, Web of Science and Cochrane Library databases were searched up to March 2022. Hazard ratios, Kaplan-Meier curves, p-values and survival outcomes were extracted. Twelve studies involving 10 583 patients were included. No significant differences in overall survival between sentinel node biopsy and elective neck dissection groups were found. Heterogeneity was not detected in pooled overall survival, disease-free survival and disease-specific survival analyses (all I2 less than 50). In subgroup analyses by follow-up period, sentinel node biopsy and elective neck dissection had similar prognostic value. Sentinel node biopsy might be a valuable alternative to elective neck dissection for the management of early stage clinically node-negative oral cavity squamous cell carcinoma.

The predictive value of depth of invasion and tumor size on risk of neck node metastasis in squamous cell carcinoma of the oral cavity: A prospective study.

Tumor depth is a reliable parameter to predict nodal metastasis in oral cancers; therefore, the authors embarked upon a prospective observational study to define the relationship between the tumor depth and the risk of cervical lymph node involvement as well to determine the optimal tumor depth cutoff point for nodal metastasis. The aim was to study the predictive value of depth of invasion (DOI) and tumor size on risk of cervical node metastasis in squamous cell carcinoma of the oral cavity. Biopsy-proven Stage I-Stage III oral cavity squamous cell carcinoma patients were included in this prospective, observational study. Various histopathological characteristics (DOI, tumor size, lympho-vascular invasion [LVI], perineural spread, and grade of differentiation) were analyzed to predict the cervical node metastasis. The impact of the clinical and histopathological parameters of primary tumor on cervical lymph node metastasis was analyzed by univariate as well as multivariate logistic regression analyses using NCSS 12 version 12.0.5 statistical software. The independent predictors of cervical lymph node metastasis were DOI (P = 0.0014) and LVI (P = 0.0414). The incidence of cervical metastasis increased markedly when the DOI was over 5 mm, and it was a statistically significant (P < 0001) association. DOI is a significant predictor of cervical nodal metastasis and tumor depth 5 mm can be considered as a cutoff value in staging and management of early oral squamous cell carcinoma.

Radiologic-pathologic correlation of major versus minor extranodal extension in oral cavity cancer.

To evaluate the diagnostic performance of radiologic extranodal extension (rENE) in predicting major (>2 mm) and minor (≤2 mm) pathologic ENE (pENE). All oral cavity squamous cell carcinoma patients who underwent neck dissection with pathological nodal disease (pN+) between 2010 and 2015 were reviewed. Preoperative computed tomography and/or magnetic resonance imaging were reviewed by two head and neck neuroradiologists. Three hundred and thirty-four patients were included. The sensitivity and specificity of rENE were 37% [95% CI 29-44] and 98% [95% CI 96-100], respectively. Sensitivity for pENE improved in the subset of patients with major ENE (48% [95% CI 38-57]). The presence of rENE was associated with inferior 3-year overall survival: 26% [95% CI 17-41] versus 60% [95% CI 54-67]. This large cohort study demonstrates high specificity, but low sensitivity for preoperative imaging in the detection of pENE in OCSCC. Patients with rENE demonstrated poor OS. pENE in the absence of rENE is still an adverse risk factor.

Patient-Derived Xenograft Engraftment Predicts Oral Cavity Cancer Outcomes

Patient-derived xenografts (PDX) can help identify oral cavity squamous cell carcinoma (OSCC) patients at risk for disease recurrence and optimize clinical decision-making. In this study, we develop and validate a prediction score for locoregional failure (LRF) and distant metastases (DM) in OSCC that incorporates PDX engraftment in addition to known clinicopathological risk factors.PDX models were generated from OSCC patients. Patients were scored as a ''non-engrafter" if PDX formation did not occur within 6 months. Multivariable analysis (MVA) was used to identify predictors of LRF and DM. Factors retained in the final MVA were used to construct a prediction score and classify patients into risk groups using a 10-fold cross-validation approach.Overall 288 OSCC patients were analyzed. MVA identified pT3-4, pENE, and engraftment as predictors of LRF and DM. Patients whose tumors engrafted (n = 198) were more likely to develop LRF (HR 1.98, 95% CI: 1.24-3.18, P < 0.01), and DM (HR 2.64, 95% CI 1.21-5.75, P < 0.01) compared to non-engrafters. A prediction score based on the aforementioned variables identified patients at high-risk (defined as having at least two of the three high risk features i.e., engraftment, pT3-4, pENE) and low-risk for LRF (43.5% vs 26.5% at 5-years, P < 0.001), DM (38.2% vs 8.4% at 5-years, P < 0.001), and poorer 5-year OS (34% vs 66%, P < 0.001). The prediction model that included engraftment had the highest discriminatory capacity in the cross-validation analysis (AUC: 67.8 [63.5-72.9]), while removal of engraftment as a predictor resulted in a lower c-index (AUC: 62.7 [57.0-68.4]). In patients classified based on a clinical score only (i.e., presence or absence of pT3-4 and pENE), engraftment remained useful in identifying those with worse outcomes. Compared to non-engrafters, engraftment was associated with higher rates of DM (15.8% vs. 5.4%, P < 0.05) in clinically "high risk" patients as well as higher rates of LRF (31.9% vs. 13.8%, P < 0.05) in clinically "low risk" patients at 5-years. Finally, engraftment was associated with poorer 5-year OS in both clinically "high risk" (36% vs. 65%, P < 0.05), and "low risk" patients (57% vs. 78%, P < 0.01).A prediction score utilizing OSCC PDX engraftment, in conjunction with pT3-4 and pENE, improves the prognostic utility of existing clinical models and predicts patients at risk for LRF, DM and poor survival.

A Consideration for Surgical Management in Select T4b Oral Cavity Squamous Cell Carcinoma.

The role of surgery for conventionally "unresectable" (cT4b) oral cavity squamous cell carcinoma is unclear. We analyzed factors associated with overall survival in cT4b relative to cT4a oral cavity squamous cell carcinoma. We identified 6830 cT4a and 522 cT4b oral cavity squamous cell carcinoma chemoradiation or surgery + adjuvant therapy patients in the National Cancer Data Base from 2004 to 2016. The main outcome was overall survival. Statistical analysis was performed using chi-squared tests, univariable and multivariable regression analysis. The cT4b group had a higher rate of positive margins (30.4% vs 21.3%, P = .009) and downstaging (41.2% vs 13.1%; P < .001) compared to cT4a, while only 1.7% were upstaged. cT4b surgery + chemoradiation patients had similar survival to cT4a surgery + radiation (HR 0.93; 95% CI, 0.70-1.25) and cT4a surgery + chemoradiation patients (HR, 0.92; 95% CI, 0.69-1.23), while cT4b surgery + radiation patients had worse OS (HR, 1.55; 95% CI, 1.05-1.47). Clinical T4b staging is a poor predictor of pathologic staging given a high rate of downstaging on final pathology. Surgical resection with adjuvant chemoradiation is an option in select cT4b oral cavity squamous cell carcinoma patients.