Oral Cavity Squamous Cell Cancer Research Articles

Poor Dental Health as a Risk Factor for Alveolar Ridge Malignancies.

To determine the association between poor dental health and risk of oral cavity squamous cell cancer (OCSCC) at individual tumor subsites. Case-control and cross-sectional METHODS: A case-control study was performed using a population-based cohort in North Carolina (Carolina Head and Neck Cancer Epidemiology Study [CHANCE]). A secondary cross-sectional analysis was performed with an institutional cohort (WashU/Siteman). Cases were adults with primary OCSCC and an identifiable tumor subsite. In the CHANCE cohort, controls were adults without head and neck cancer. In the Washington University/Siteman cohort, patients with tongue cancer served as the comparator group. We used number of missing teeth (categorized 0-6, 7-24, 25-28) as a surrogate for poor dental health, which was self-reported in CHANCE and measured on a pretreatment computed tomography scan in the WashU/Siteman study. Adjusted odds ratios (aORs) for missing teeth were estimated for each tumor subsite using binomial logistic regression models. Near complete tooth loss (25-28 teeth) was associated with a 3.5-fold increased risk of alveolar ridge malignancy (aOR: 3.51; 95% confidence interval [CI]: 1.14-11.01, P = .03) in the CHANCE study. This association was confirmed in our cross-sectional analysis (WashU/Siteman study) where missing 25-28 teeth was associated with an increased risk of alveolar ridge compared to tongue cancer (aOR: 4.60; 95% CI: 1.97-11.10, P = .001). This study suggests an association between poor dental health and risk of alveolar ridge cancer independent of smoking, alcohol use, age, race, and sex. Future prospective and translational studies are needed to confirm this association and elucidate the mechanism of dental disease in alveolar ridge malignancies.

144P Correlation of EZH2 expression and response to chemoradiotherapy in patients with locally advanced inoperable oral cavity and oropharyngeal squamous cell cancers

144P Correlation of EZH2 expression and response to chemoradiotherapy in patients with locally advanced inoperable oral cavity and oropharyngeal squamous cell cancers

Image-Guided Intraoperative Assessment of Surgical Margins in Oral Cavity Squamous Cell Cancer: A Diagnostic Test Accuracy Review.

(1) Background: The assessment of resection margins during surgery of oral cavity squamous cell cancer (OCSCC) dramatically impacts the prognosis of the patient as well as the need for adjuvant treatment in the future. Currently there is an unmet need to improve OCSCC surgical margins which appear to be involved in around 45% cases. Intraoperative imaging techniques, magnetic resonance imaging (MRI) and intraoral ultrasound (ioUS), have emerged as promising tools in guiding surgical resection, although the number of studies available on this subject is still low. The aim of this diagnostic test accuracy (DTA) review is to investigate the accuracy of intraoperative imaging in the assessment of OCSCC margins. (2) Methods: By using the Cochrane-supported platform Review Manager version 5.4, a systematic search was performed on the online databases MEDLINE-EMBASE-CENTRAL using the keywords "oral cavity cancer, squamous cell carcinoma, tongue cancer, surgical margins, magnetic resonance imaging, intraoperative, intra-oral ultrasound". (3) Results: Ten papers were identified for full-text analysis. The negative predictive value (cutoff < 5 mm) for ioUS ranged from 0.55 to 0.91, that of MRI ranged from 0.5 to 0.91; accuracy analysis performed on four selected studies showed a sensitivity ranging from 0.07 to 0.75 and specificity ranging from 0.81 to 1. Image guidance allowed for a mean improvement in free margin resection of 35%. (4) Conclusions: IoUS shows comparable accuracy to that of ex vivo MRI for the assessment of close and involved surgical margins, and should be preferred as the more affordable and reproducible technique. Both techniques showed higher diagnostic yield if applied to early OCSCC (T1-T2 stages), and when histology is favorable.

Imaging Recommendations for Diagnosis, Staging, and Management of Oral Cancer

AbstractOral cavity cancers contribute to a majority of cancers in India. Clinical examination alone cannot determine the deeper extent of the disease; therefore, need for cross-sectional imaging including computed tomography and magnetic resonance imaging becomes indispensable for pre-treatment evaluation to decide optimal plan of management. Oral cavity squamous cell cancers (OSCC) can be treated with surgery alone, whereas deep muscle, neurovascular, osseous, or nodal involvement on imaging suggests advanced disease that requires a combination of surgery, radiation, and/or chemotherapy. Because of the complex anatomy of the oral cavity and its surrounding structures, imaging is crucial for locoregional staging and early detection of distant metastases. Imaging plays indispensable role not only in diagnosis but also in planning the management. An optimal guideline paper for developing countries like India is lacking that not only helps standardize the management but will also assist oncologists make reasonable decisions and reduce the unnecessary imaging. This imaging guideline paper will discuss the optimal imaging in diagnosis and management OSCC for Indian subcontinent.

Active upper aerodigestive tract hemorrhage in patients with head and neck cancers: the “dot-in-sludge” sign

Active extravasation into the upper aerodigestive tract is a dramatic and potentially life-threatening complication in patients with head and neck cancers. It prompts presentation to the emergency room and subsequent urgent imaging to identify the source of hemorrhage. Imaging of these patients may be complicated by treatment-altered anatomy, posing a challenge to the emergency radiologist who needs to rapidly identify the presence of active hemorrhage and the potential source vessel. This retrospective review summarizes the clinical and imaging findings of 6 oropharyngeal and oral cavity squamous cell cancer (SCC) patients with active upper aerodigestive tract hemorrhage. Most patients had advanced stage disease and prior radiation therapy. All CECT or CTA exams on presentation demonstrated the “dot-in-sludge” sign of active extravasation, as demonstrated by a “dot” of avidly enhancing extravasated contrast material layered against a background “sludge” of non-enhancing debris in the lumen of the upper aerodigestive tract. Common sources of hemorrhage included the lingual, facial, and superior thyroidal arteries. Familiarity with these findings will help radiologists increase their accuracy and confidence in interpreting these urgent, complex examinations.

Surgical anatomy of the lingual lymph nodes: systematic literature analysis and proposition for topographic classification.

Metastatic involvement of the lingual lymph nodes (LLNs) in oral cavity squamous cell cancer (SCC) has recently been proven to significantly reduce locoregional control and survival. Despite recent refinements in the detection of these lesions, the understanding of the LLN topographic anatomy among clinicians is limited. A proposition of a topographic division on LLN based on a comprehensive literature search and synthesis may be helpful in this condition. A literature search and election based on contemporary PRISMA guidelines was performed for sources on LLN anatomy with special attention on their subdivision. Four topographic LLN subgroups were defined: median-between genioglossal and geniohyoid muscles; intermediate parahyoid-medial to the hyoglossal muscle, at the greater cornu of the hyoid bone; lateral sublingual (paraglandular) LLNs-at the sublingual salivary gland; lateral submandibular (paraglandular) LLNs -lateral to the hyoglossal muscle, at the deep surface of the submandibular salivary gland. The development and implementation of a unified anatomical topographic classification of LLN subgroups may be among the important conditions for improving the detection and treatment of LLN lesions.

Phase 2, randomized, double-blind trial of EC-18 versus placebo to mitigate the development and time course of oral mucositis from concomitant chemoradiation for head and neck cancer.

12106 Background: Oral mucositis (OM) is a debilitating side effect of concomitant chemoradiotherapy (CRT) for head and neck cancer (HNC). EC-18 may effectively mitigate OM by minimizing the CRT-induced innate immune response. This Phase II, 2-stage trial evaluated safety, tolerability, and efficacy of EC-18 in reducing the duration, incidence, and trajectory of severe OM (SOM) in HNC patients. Methods: Patients (n = 105) with pathologically confirmed oral cavity, oropharynx, hypopharynx, or nasopharynx squamous cell cancers who received intensity-modulated radiation therapy (IMRT; with ≥ 55 Gy on ≥ 2 oral sites) and weekly or tri-weekly cisplatin were studied. In Stage 1, 24 patients were randomized (n = 6 per arm) to receive 500, 1000, or 2000 mg of EC-18, or placebo. Following independent Data Safety Monitoring Board review, 81 patients in Stage 2 received EC-18 2000 mg (n = 41) or placebo (n = 40) throughout CRT. WHO OM grade was assessed twice weekly during IMRT and then once weekly for up to 6 weeks post-IMRT. The primary efficacy endpoint was duration of SOM during the active and short-term follow-up (STFU) periods in the compliant per-protocol population (PP). Much of Stage 2 was conducted during peak periods of the COVID-19 pandemic which measurably impacted patient compliance relative to test medication dosing and planned radiation. Consequently, to assess efficacy most accurately, the PP population was analyzed (with at least 4 weeks of study drug dosing, minimum cumulative radiation of 55 Gy, 80% study drug compliance in the first 28 days of dosing, and without using not-allowed-therapy). Results: Patient demographics and baseline characteristics were balanced between groups. Adverse events (AEs) were comparable amongst cohorts without drug-related severe AEs. In the PP, the median duration of SOM from baseline through STFU was 0 day in the EC-18 group (n = 22) v 13.5 days in the placebo group (n = 20). SOM incidence through STFU (45.5% v 70%) and opioid use (time to onset: 32.3 v 26.0 days; and duration: 32.8 v 37.5 days) favored EC-18 v placebo. Results of the covariates analyses suggested that EC-18 favorably impacted SOM incidence in patients who experienced SOM treated with weekly low-dose cisplatin (n = 26; 37.5% v placebo 70.0%) and HPV+ tumors (n = 29; 35.3% v placebo 66.7%; Table). One-year long-term follow-up for tumor outcomes is ongoing. Conclusions: EC-18 safely mitigated the development and the time course of SOM in CRT-treated HNC patients. In addition, EC-18 may provide substantial benefits to subpopulations of HPV+ HNC patients treated with low dose cisplatin. Clinical trial information: NCT03200340. [Table: see text]

Omission of the Pathologic Node-Negative Neck From Postoperative Radiation Therapy for Oral Cavity Cancer

<h3>Purpose/Objective(s)</h3> Elective neck dissection has been shown to confer a survival benefit in the setting of oral cavity squamous cell cancer (OC-SCC). Post-operative radiation therapy (RT) is recommended after primary surgical management of OC-SCC for adverse pathologic features. Current guidelines recommend coverage of the operative bed, including the pathologic node-negative (pN0) neck, which is associated with worse late toxicity and quality of life. The risk of regional failure with omission of the pN0 neck from the RT treatment volume is not well described. <h3>Materials/Methods</h3> Patients (pts) with OC-SCC who underwent primary surgical management and were treated with post-operative RT at a single institution between 2011 and 2019 were retrospectively analyzed. Intensity-modulated RT was used in all cases. Post-operative RT was delivered once daily. Post-operative chemoradiation therapy (CRT) typically consisted of concomitant fluorouracil, hydroxyurea, with or without paclitaxel in a week-on/week-off fashion with either once- or twice-daily RT. The Kaplan-Meier method was used to estimate rates of local failure-free survival (LFFS), omitted neck failure-free survival (ONFFS), distant metastasis-free survival (DMFS), and overall survival. Cox regression analysis was used to examine the relationships between clinicopathologic variables, and ONFFS. <h3>Results</h3> 47 pN0 hemi-necks in 36 pts were omitted from the post-operative RT treatment volume. The median follow-up was 53.5 months. Primary site was oral tongue in the majority (N = 16). Other subsites included floor of mouth (N = 7), alveolus (N = 6), buccal (N = 3), retromolar trigone (N = 1), and palate (N = 1). Median number of lymph nodes removed from the RT-omitted pN0 ipsilateral and contralateral hemi-neck were 24 (IQR: 19-27) and 18.5 (IQR: 9-24), respectively. Perineural invasion was present in 63% and lymphovascular invasion was present in 18%. T-stage was T1 (N = 4), T2 (N = 10), T3 (N = 7), and T4 (N = 15). Overall N-stage (including the pathologic node-positive hemi-neck, if present) was N0 (N = 23), N1 (N = 5), N2a (N = 1), N2b (N = 2), and N3b (N = 5). Median RT dose was 66 Gy (IQR: 60-66). 70% of pts received concurrent CRT. 89% of pts received once-daily RT and 11% received twice-daily RT. Overall, three hemi-necks (6%) in three pts (8%) were found to have omitted neck relapse. Two-year LFFS, ONFFS, DMFS, and OS were 97%, 91%, 94%, and 92%, respectively. Four-year LFFS, ONFFS, DMFS, and OS were 93%, 91%, 91%, and 85%, respectively. On Cox regression, floor of mouth subsite (FOM) (HR 11.1 [C.I.: 1.0-126.2], p=0.05) was associated with an increased risk of ONFFS. <h3>Conclusion</h3> In this largest reported series of OC-SCC pts treated with post-operative RT omitting the pN0 neck, low rates of regional failures occurred overall.

Oral cavity squamous cell carcinomas in patients with no identified risk factors: Feeling like an outsider.

Head and neck squamous cell carcinomas (HNSCCs) mainly affect smokers and drinkers. However, oral cavity squamous cell cancers (OCSCCs) are increasingly affecting patients with no identified risk factors (NIRFs). This study aimed at characterising their experience of the disease. Qualitative study based on semi-structured interviews of 20 survivors of OCSCC with NIRF. Methods used in grounded theory approach were applied. Patients with NIRF had a similar experience to that of patients with risk factors regarding treatments. The absence of identified causes led to stigma and led the patients to distance themselves, both from the stereotypic HNSCC cancer patient and the identity as a cancer patient. Furthermore, having no identified risk factors seemed to reinforce the fear of recurrence. This study is the first to address key gaps in knowledge regarding patients with NIRF having survived OCSCC. Their experience is similar to that of patients with orphan diseases. Owing to confrontation with other patients and the repeated questions of caregivers about tobacco/alcohol consumption, these patients felt stigmatised during their treatment. OCSCC patients with NIRF may benefit from guidance and support on how to engage in prevention.

Use of Fluoro-[18F]-Deoxy-2-D-Glucose Positron Emission Tomography/Computed Tomography to Predict Immunotherapy Treatment Response in Patients With Squamous Cell Oral Cavity Cancers

Neoadjuvant immunotherapy is a novel approach with the potential to improve outcomes for patients with oral cavity squamous cell cancer (OCSCC). Adverse events of varying severity are reported with immunotherapy, and a biomarker to predict response would be clinically useful to avoid toxic effects in those unlikely to benefit. To correlate changes on fluoro-[18F]-deoxy-2-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) scans with primary tumor pathologic response and immunologic biomarkers in patients with OCSCC receiving neoadjuvant immunotherapy. This was a retrospective analysis of serial FDG-PET/CT scans obtained prospectively as part of a phase 2 open-label randomized clinical trial investigating neoadjuvant immunotherapy in patients with untreated OCSCC between 2016 and 2019. Included were a total of 29 patients from a single academic medical center with untreated OCSCC (≥T2, or clinically node positive) randomized 1:1 to receive neoadjuvant therapy with single agent nivolumab or combination nivolumab and ipilimumab followed by surgery and standard of care adjuvant therapy. The interventions in this study were FDG-PET/CT scans before (T0) and after (T1) preoperative immunotherapy. Data collected from FDG-PET/CT scans included maximum standardized uptake value (SUVmax) of primary OCSCC and cervical lymph nodes (LNs) at T0 and T1 and new LN uptake and uptake consistent with radiologic immune-related adverse events (irAEs) at T1. Primary OCSCC pathologic response reported as percentages of viable vs nonviable tumor. The number of CD8+ cells/mm2 was determined in the primary tumor biopsy specimen and at surgery. There was no correlation between pathologic response and change in SUVmax in the primary OCSCC between T0 and T1. Out of 27 total participants, 13 had newly FDG-avid ipsilateral LNs at T1, most negative on pathology. A total of 9 had radiologic irAEs, most commonly sarcoid-like LN (7 of 27). No correlations were found between primary OCSCC SUVmax at T0 and CD8+ T-cell number in the primary tumor biopsy, and no correlations were found between primary OCSCC SUVmax at T1 and CD8+ T-cell number in the primary tumor at surgery. There were no correlations between changes in FDG uptake after neoadjuvant immunotherapy and pathologic primary tumor response. Importantly, newly FDG-avid ipsilateral LNs following neoadjuvant immunotherapy were commonly observed but did not represent progressive disease or indicate pathologically disease positive nodes in most cases. These findings argue against altering surgical plans in this setting and suggest that the role of FDG-PET/CT may be limited as an early imaging biomarker for predicting pathologic response to preoperative immunotherapy for OCSCC. ClinicalTrials.gov Identifier: NCT02919683.

Results from a prospective, randomised study on (accelerated) preoperative versus (conventional) postoperative radiotherapy in treatment of patients with resectable squamous cell carcinoma of the oral cavity – The ARTSCAN 2 study

Background and purposeAn earlier prospective randomised multicentre study (ARTSCAN) in head and neck cancer patients that compared conventionally fractionated radiotherapy (CF) with accelerated radiotherapy (AF) was inconclusive. In the subgroup of oral cavity squamous cell cancer (OCSCC) a large absolute, but not statistically significant, difference in local control was seen in favour of AF. This difference was more pronounced in resectable tumours. The finding raised the hypothesis that AF could be beneficial for OCSCC patients. In addition, the longstanding controversy on pre- or postoperative radiotherapy was addressed. Materials and methodsPatients with OCSCC, judged to withstand and likely benefit from combined therapy, were recruited. Subjects were randomised to either preoperative AF with 43 fractions given as a concomitant boost with two fractions/day to the tumour bearing volume to a total dose of 68 Gy in 4.5 weeks followed by surgery, or primary surgery with postoperative CF, total dose 60 or 66 Gy in 6–7 weeks. For patients whose tumours had high-risk features, 66 Gy and concomitant cisplatin was prescribed. Results250 patients were randomised. Median follow-up was 5 years for locoregional control (LRC) and 9 years for overall survival (OS). There were no statistically significant differences between the two treatment arms regarding LRC and OS. LRC at five years was 73% (95% CI, 65–82) in preoperative AF and 78% (95% CI, 70–85) in postoperative CF.Toxicity was more pronounced in preoperative AF. ConclusionThis study does not support that AF prior to surgery improves outcome in oral cavity cancer compared with postoperative CF.

Prognostic Value of Lymph Node Density in Node-Positive Oral Squamous Cell Carcinoma.

Lymph node status is an important prognostic factor in head and neck cancer. The purpose of this study is to investigate the prognostic value of lymph node density (LND) in node-positive oral cavity cancer patients who received surgery plus adjuvant radiotherapy. From January 2008 to December 2013, a total of 61 oral cavity squamous cell cancer patients who had positive lymph node and received surgery and adjuvant radiotherapy were analysed. LND was calculated for each patient. The endpoints were 5-year overall survival (OS) and 5-year disease-free survival. All patients were followed for a period of 5years. Mean 5-year overall survival for cases with LND of ≤ 0.05 was 56.1 ± 11.6months, whereas mean 5-year overall survival for cases with LND > 0.05 was 40.0 ± 21.6months. Log rank is 0.04 95% CI = 53.4-65. Mean 5-year disease-free survival for cases with LND of ≤ 0.05 was 50.5 ± 15.8months, whereas mean disease-free survival for cases with LND > 0.05 was 15.8 ± 22.9months. Log rank 0.03 95% CI = 43.3-57.6. Nodal status, disease stage and lymph node density were found to be significant predictors of prognosis in univariate analysis. In multivariate analysis, only lymph node density is found to be the predictor of prognosis. LND is an important prognosis factor for 5-year OS and 5-year DFS in oral cavity squamous cell carcinoma.

The Potential Impact and Usability of the Eighth Edition TNM Staging Classification in Oral Cavity Cancer

AimsIn the current eighth edition head and neck TNM staging, extranodal extension (ENE) is an adverse feature in oral cavity squamous cell cancer (OSCC). The previous seventh edition N1 with ENE is now staged as N2a. Seventh edition N2+ with ENE is staged as N3b in the eighth edition. We evaluated its potential impact on patients treated with surgery and postoperative intensity-modulated radiotherapy (IMRT). Materials and methodsOSCC patients treated with primary surgery and adjuvant (chemo)radiotherapy between January 2005 and December 2014 were reviewed. Cohorts with pathological node-negative (pN–), pathological node-positive without ENE (pN+_pENE–) and pathological node-positive with ENE (pN+_pENE+) diseases were compared for local control, regional control, distant control and overall survival. The pN+ cohorts were further stratified into seventh edition N-staging subgroups for outcomes comparison. ResultsIn total, 478 patients were evaluated: 173 pN–; 159 pN+_pENE–; 146 pN+_pENE+. Outcomes at 5 years were: local control was identical (78%) in all cohorts (P = 0.892), whereas regional control was 91%, 80% and 68%, respectively (P < 0.001). Distant control was 97%, 87%, 68% (P < 0.001) and overall survival was 75%, 53% and 39% (P < 0.001), respectively. Overall survival for N1 and N2a subgroups was not significantly different. In the seventh edition N2b subgroup of pENE– (n = 79) and pENE+ (n = 79) cohorts, overall survival was 67% and 37%, respectively. In the seventh edition N2c subgroups, overall survival for pENE– (n = 17) and pENE+ (n = 38) cohorts was 65% and 35% (P = 0.08), respectively. Overall, an additional 128 patients (42% pN+) were upstaged as N3b. ConclusionsWhen eighth edition staging was applied, stage migration across the N2–3 categories resulted in expected larger separations of overall survival by stage. Patients treated with primary radiation without surgical staging should have outcomes carefully monitored. Strategies to predict ENE preoperatively and trials to improve the outcomes of pENE+ patients should be explored.

Abstract 2986: Conditional reprogramming of primary head and neck tumor cells to establish consistent and diverse cell line models

Abstract Introduction Head and neck squamous cell carcinoma (HNSCC) most commonly arise in the oral cavity, pharynx, and larynx and exhibit diverse molecular characteristics and clinical behavior across sites. Current models of HNSCC largely rely on immortalized cell lines, which suffer from selection bias and clonality. Primary cell cultures, on the other hand, are difficult to maintain and are limited by their finite ability to proliferate. Here, we describe the establishment of a robust HNSCC cell line bank using a “conditional reprogramming” (CR) method which relies on treatment with a rho kinase inhibitor (Y-27632) and co-culture with irradiated fibroblast (J2 strain) feeder cells to support indefinite tumor cell survival. Methods HNSCC tumors were acquired on an IRB-approved prospective tissue banking protocol. Tumor tissue and blood were collected from each patient, and tumor cells were digested and cultured using previously described CR methods. DNA was collected from tumor tissue and CR cultures and short tandem repeat (STR) profiling was used to validate culture against patient tumor tissue. To verify that the cultures were of squamous origin, western blot analysis was used to detect cytokeratin 5, cytokeratin 6 and p63. Tumor cell phenotype and growth characteristics were examined with light microscopy. HPV testing was carried out on DNA from CR cultures and matched tumor samples using PCR and specific genotyping by oligonucleotide hybridization. HPV testing was correlated with clinical p16 testing results. Whole exome sequencing was carried out on a subset of blood/tumor/CR culture samples. Results Eighteen CR lines were successfully cultured and validated with STR genotyping from 25 sequentially procured tumors. 10/18 were derived from oral cavity squamous cell cancers (SCCs), 5/18 were derived from oropharyngeal SCCs, and 3/18 were derived from laryngeal SCCs. 18/18 lines were found to express p63 and either cytokeratin 5 or 6, verifying these cultures contained tumor cells of squamous origin. 4/5 tumors from oropharyngeal SCCs were p16-positive on clinical testing and considered HPV-mediated. These 4 tumors all tested positive for HPV DNA in both tumor samples and CR cultures. Preliminary comparison of exome sequencing results between CR cultures and primary tumors suggests that overall mutational profiles are preserved through the tumor “conditional programming” process. Tumor heterogeneity between original tumor and CR culture is being actively compared in ongoing analyses. Conclusion We have consistently generated primary tumor CR cultures from patients with HNSCC arising in three major anatomical subsites of HNSCC disease, including HPV-mediated tumors. CR methods can be readily applied to all HNSCC tumors regardless of disease site and molecular background, providing a translational research model that can capture the molecular and phenotypic breadth of HNSCC disease. Citation Format: Daniel Li, Carlos Thomas, Nitisha Shrivastava, Nicholas Gadsden, Nicole Kawachi, Bradley A. Schiff, Richard V. Smith, Nicolas F. Schlecht, Michael B. Prystowsky, Gregory Rosenblatt, Stelby Augustine, Chandan Guha, Evripidis Gavathiotis, Robert D. Burk, Vikas Mehta, Thomas J. Ow. Conditional reprogramming of primary head and neck tumor cells to establish consistent and diverse cell line models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2986.

Addressing the contralateral neck for ipsilateral disease recurrence in oral cavity cancers

BackgroundEvidence for performing contralateral neck dissection (CND) of recurrent oral cavity squamous cell cancers (OCSCC) is lacking. Material and methodsThis is a retrospective study of 78 consecutive OCSCC having ipsilateral recurrence recorded over five years. We screened 1658 OCSCC patients and selected those patients who underwent CND as part of treatment for ipsilateral recurrence. ResultsThe median disease-free interval was 32 months. Incidence of contralateral nodal metastasis (CNM) in recurrent OCSCC was 23.1% and of which 14% were occult. The factor significantly influencing CNM was the depth of invasion (DOI) > 10 mm (p < 0.01). In our study, imaging had suboptimal PPV (33%) while it had high NPV (88%) in diagnosing nodal metastasis in recurrent OCSCC. ConclusionDOI is the most important factor predicting CNM in case of ipsilateral primary recurrence. PET-CECT has a high NPV and contralateral neck should be addressed in case of tumours with higher DOI.

Non-operative management for oral cavity carcinoma: Definitive radiation therapy as a potential alternative treatment approach

PurposeTo determine the outcomes of oral cavity squamous cell cancer (OSCC) patients treated with non-surgical approach i.e. definitive intensity-modulated radiation therapy (IMRT). MethodsAll OSCC patients treated radically with IMRT (without primary surgery) between 2005–2014 were reviewed in a prospectively collected database. OSCC patients treated with definitive RT received concurrent chemotherapy except for early stage patients or those who declined or were unfit for chemotherapy. The 5-year local, and regional, distant control rates, disease-free, overall, and cancer-specific survival, and late toxicity were analyzed. ResultsAmong 1316 OSCC patients treated with curative-intent; 108 patients (8%) received non-operative management due to: medical inoperability (n = 14, 13%), surgical unresectability (n = 8, 7%), patient declined surgery (n = 15, 14%), attempted preservation of oral structure/function in view of required extensive surgery (n = 53, 49%) or extensive oropharyngeal involvement (n = 18, 17%). Sixty-eight (63%) were cT3-4, 38 (35%) were cN2-3, and 38 (35%) received concurrent chemotherapy. With a median follow-up of 52 months, the 5-year local, regional, distant control rate, disease-free, overall, and cancer-specific survival were 78%, 92%, 90%, 42%, 50%, and 76% respectively. Patients with cN2-3 had higher rate of 5-year distant metastasis (24% vs 3%, p = 0.001), with detrimental impact on DFS (p = 0.03) and OS (p < 0.02) on multivariable analysis. Grade ≥ 3 late toxicity was reported in 9% of patients (most common: grade 3 osteoradionecrosis in 6%). ConclusionsNon-operative management of OSCC resulted in a meaningful rate of locoregional control, and could be an alternative curative approach when primary surgery would be declined, unsuitable or unacceptably delayed.

A review of head and neck squamous cell carcinoma response to taxane chemotherapy treatment in the pre versus post nivolumab era.

e18504 Background: Nivolumab received FDA approval as monotherapy for the treatment of recurrent or metastatic squamous cell carcinoma (SCC) of the head and neck after failure of platinum-based therapy in 2016. This approval was based on CheckMate 141. When patients ultimately relapse after immunotherapy in the second line setting, third line agents include single agent or combination treatment with a Taxane. Methods: We identified patients with metastatic or recurrent squamous cell head and neck cancer in an Irish hospital who had received Taxane chemotherapy after immunotherapy. We looked at outcomes for these patients including progression free survival (PFS) and overall survival (OS). We then identified a group of patients who received a Taxane following platinum failure in the pre-Nivolumab era to act as a comparator. Our objective was to compare PFS and OS to subsequent Taxane chemotherapy in the era before and after the introduction of Nivolumab as a therapy for platinum refractory head and neck SCC. Results: This retrospective cohort study was made up of 26 patients with metastatic or recurrent head and neck cancer. Primary sites included oropharynx, oral cavity, larynx and nasal cavity squamous cell cancers. The patients had a median age of 56. 13 of these patients identified had progressed on Nivolumab but remained fit for a next line of treatment. Median PFS in this group on Taxane based chemotherapy in the third line setting was 3.8 months. Median OS post progression on Nivolumab was 10 months. One patient remarkably had a complete response to Paclitaxel chemotherapy after progression on previous lines of treatment including immunotherapy, platinum chemotherapy and radiotherapy. We then identified a group of 13 patients with metastatic or recurrent head and neck cancer that had progressed on platinum based therapy in the era before Nivolumab was available. Median PFS after Taxane second line chemotherapy was 2.2 months. Median OS in this group after progressing on platinum treatment was 5.8 months. Conclusions: We set out to share our experience of real-world outcomes for head and neck cancer patients in the Nivolumab era. We found that our patients have shown to have an improved overall survival benefit with subsequent Taxane chemotherapy after immunotherapy compared to those who have not received immunotherapy. All fit patients should be considered for Taxane therapy post failure of Nivolumab.

Free radial forearm flap for reconstruction of postoperative defects in combined and complex treatment of patients with locally-advanced squamous cell carcinoma of the oral cavity

The study objectiveis to assess immediate and long-term results of replacing complex defects with a free radial forearm flap in the multimodal treatment of patients with locally advanced oral cavity squamous cell carcinoma.Materials and methods.Twenty eight patients (20 women and 8 men aged 23 to 71 years) with locally advanced oral cavity squamous cell carcinoma (including 10 buccal cancers, 8 carcinomas of tongue, 6 carcinomas of the floor of the mouth, 2 retromolar area carcinomas, 1 carcinoma of the hard palate and 1 carcinoma of alveolar region of the lower jaw) underwent tumor surgery with simultaneous plastic reconstruction of the defect using radial forearm free flap at the department of head and neck tumors of N. N. Blokhin National Medical Research Center of Oncology within 2010–2018. Primary tumors were detected in 2 patients and 11 patients had residual (n = 7) or recurrent (n = 4) tumors after radiotherapy or chemoradiotherapy.Results.An overall success rate was 96.4 %. Postoperative histology revealed that there were no tumor cells at the resection edges. Postoperative complications included: complete flap necrosis in 1 patient with severe concomitant diseases, marginal flap necrosis in 2 patients (in both cases after the necrotic tissue had rejected, wounds were healed by secondary intention), sural veins thrombosis in 1 patient, acute peptic ulcer bleeding on the 6th day after surgery in 1 patient treated with emergency endoscopic hemostasis. No lethal outcomes were reported. Postoperative period lasted in average 14 days. Upon subsequent observation tumor relapse in the oral cavity occurred in 4 (14.3 %) patients, relapses of regional metastases – in 2 (7.1 %). Good aesthetic and functional results were noted. Adequate restoration of breathing, chewing, swallowing and speaking resulted in a full patients’ rehabilitation. In all cases, the radial flap adapted well to the oral cavity organs and corresponded to the surrounding tissues in thickness and consistency.Conclusion.Use of a radial forearm free flap makes it possible to successfully reconstruct extensive and complex defects after surgery of locally advanced primary and recurrent forms of oral cavity squamous cell cancer of various locations. Due to flap’s high regenerative capabilities, preoperative radiation therapy does not affect the frequency of local complications. It allows restoring vital functions of the oral cavity and achieving good aesthetic and functional results.

Tongue flap- a good choice for intraoral reconstruction after marginal mandibulectomy: a single institution retrospective study of 27 cases

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Marginal mandibulectomy with wide excision of the primary tumour in the treatment of the oral cavity squamous cell cancers preserves the form and function of the mandible, without compromise in obtaining oncologically safe margins. Of the various methods of reconstruction of the composite intraoral tissue defect, tongue flaps offer an easy and effective method of reconstruction.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; We have collected the records of 27 patients who underwent marginal mandibulectomy and tongue flap reconstruction in the last 6 years from the cancer department master case sheets, operative records and follow up records. The information on the immediate and long term complications were obtained from the records and functional outcomes of patients were recorded at the time of last follow up and analysed. All the 27 patients had horizontal marginal mandibulectomy with an anteriorly or posteriorly based tongue flap reconstruction. &lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; The most common early postoperative complication was infection around the flap site that occurred in 18.5% of patients. The other complications including haemorrhage, flap dehiscence occurred in few patients which were managed effectively. There was no incidence of major flap necrosis. Speech and swallowing difficulty was encountered in 18.5% and 14.8% of patients respectively. The long term complications were managed conservatively with speech and swallowing therapy.&lt;/p&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt;In our experience, tongue is an excellent donor site for intraoral soft tissue reconstruction, providing an analogous tissue for reconstruction. The technique is simple with acceptable rates of immediate and long term complications and with good functional outcomes.&lt;p&gt; &lt;/p&gt;

Nomogram Identifies Age as the Most Important Predictor of Overall Survival in Oral Cavity Squamous Cell Cancer After Primary Surgery.

Our goal was to determine the most important predictors and construct a nomogram for overall survival (OS) in oral cavity squamous cell cancer (OCSCC) treated with primary surgery followed by observation, adjuvant radiation or chemoradiation. Multivariable analysis was performed using Cox Proportional Hazard model of 9258 OCSCC patients from Surveillance, Epidemiology and End Results Program (SEER) database treated with surgery from 2003 to 2009. Potential predictors of OS were age, gender, race, tobacco use, oral cancer sub-sites, pathologic tumor stage and grade, pathologic nodal stage, extra-capsular invasion, clinical levels IV and V involvement, and adjuvant treatment selection. Weighted propensity scores for treatment were used to balance observed baseline characteristics between three treatment groups in order to reduce bias. Following primary surgery, patients underwent observation (56%), radiation alone (31%) or chemoradiation (13%). All tested predictors were statistically significant and included in our final nomogram. Most important predictor of OS was age, followed by pathologic tumor stage. SEER based-survival nomogram for OCSCC patients differs from published models derived from patients treated in a single or few academic treatment centers. An unexpected finding of patient age being the best OS predictor suggests that this factor may be more critical for the outcome than previously anticipated.