Oral Cavity Squamous Carcinoma Research Articles

Challenges in the Assessment of Medullary Bone Invasion in Oral Cavity Cancers and Its Prognostic Significance.

As per AJCC 8th edition TNM staging system, bone invasion is a poor prognostic marker that upstages oral cavity squamous carcinoma (OSCC) to pT4a. Cortical erosion alone of bone or tooth socket by a gingival primary is not sufficient to upstage a tumour. The differentiation of cortical erosion from invasion through the cortical bone into the medulla is often challenging, limiting accurate staging. This review aims to assess the difficulties in differentiating cortical erosion from medullary invasion and evaluate the prognostic significance of different patterns of bone involvement. A retrospective review of OSCC with primary curative surgery and bone resection treated at a single-center over 10years, was performed to assess the prognostic significance of bone invasion. Hematoxylin-eosin stained slides of a subset of cases were re-reviewed in a planned manner to assess difficulties in precise categorization (no invasion/erosion/cortical invasion and medullary invasion), evaluate interobserver agreement, and correlate with clinical outcome. Five hundred and ninety patients were included, with a median follow-up of 28months. On univariate analysis, the 3-year local, nodal and distant metastasis control were not significantly different in the 3 groups of no invasion, erosion, and invasion (p = 0.43, 0.47, and 0.47, respectively). Overall survival (OS) at 3years was 78.1% and disease-free-survival(DFS) was 63.7% in the entire cohort. On univariate analysis, there was significant difference in OS and DFS based on these groups. This did not translate into independent prognostic benefit on multivariable analysis (p = 0.75 and 0.19, respectively). The independent prognostic factors were margin positivity, tumor differentiation, perineural invasion and pathological nodal involvement. Planned re-review of a subset of 202 cases resulted in a change in bone involvement category in 26/202 cases, which was mainly due to difficulty in assessing cortico-medullary junction near the tooth socket and bone fragmentation. The assessment showed moderate to near complete agreement (kappa 0.59-0.82) between 2 observers. Our study shows that bone involvement is not an independent prognostic marker and there is no specific correlation of medullary invasion with outcome over those that showed cortical erosion. Several factors contribute to difficulties and interobserver variability in assessing bone involvement.

Role of Selective Neck Dissection in Clinically Single Node Positive Disease in Oral Cavity Cancers.

Management of the neck in oral cavity squamous carcinoma is debatable. There is controversy regarding role of SND in single node positive neck in oral SCC. The aim of this study was to determine the efficacy of selective neck dissection (SND) for cN1 neck in patients with oral cancer. A retrospective chart review of 266 oral cancer patients who were clinically single node positive from August 2013 to December 2019 was done. Patients having clinical or radiological cN1 disease undergoing SND were included. Two hundred sixty-six patients were analysed with 86% male predominance. Median age was 48years. The commonest primary site was Bucco-alveolar complex (64%). Total of 319 SNDs were done in 266 patients. At median follow-up of 29months, 29 patients (9%) had neck recurrence among which 4 patients had recurrence at level V, along with recurrence at other nodal levels. Three-year regional control was 86%, while DFS and OS were 66% and 68% respectively. For oral cancer with single clinically node positive neck (cN1), SND is an effective and oncological safe treatment. Outcomes are similar with modified neck dissection reported in the literature.

Abstract 2514: Cell-free chromatin particles released into the microenvironment from dying tumor cells activate cancer hallmarks in surviving cells: a study in advanced squamous cell carcinoma of oral cavity with therapeutic implications

Abstract Background: We have reported that combination of the nutraceuticals Resveratrol (R) and Copper(Cu) results in generation of free radicals which can degrade cell-free chromatin (cfCh) particles and have potential therapeutic effects (Mittra et al., Ann. Oncol. 2017 & Mittra et al., PLos One 2020). We have also reported that cfCh particles that are released from dying tumor cells can integrate into genomes of healthy bystander cells to activate two critical hallmarks of cancer namely, genome instability and inflammation, which could lead to their oncogenic transformation (Mittra et al., Cell Death Discovery 2017). Here we show that cfCh particles released into tumor microenvironment (TME) from dying tumor cells of advanced squamous carcinoma of oral cavity activate all ten hallmarks of cancer defined by Hanahan and Weinberg, and that oral administration of R-Cu for two weeks prevents this potentially life-threatening manifestation. Patients and Methods: The study was approved by Institutional Ethics Committee, and a written consent was obtained from participants. In this exploratory study, R-Cu was administered in four escalating doses orally for two weeks, to 25 patients divided into 5 groups with 5 patients each, as follows: 1) Control: R 0, Cu 0; 2) Level I: R 5.6 mg, Cu 560 ng; 3) Level II: R 50 mg, Cu 5µg; 4) Level III: R 500 mg, Cu 50 µg; 5) Level IV: R 500 mg, Cu 5mg. A punch biopsy was obtained on the day 0 and day 14 post R-Cu treatment. FFPE histological sections were examined by 1) Fluorescence immuno-staining (FI) using anti-DNA and anti-histone H4 antibodies and confocal microscopy to detect presence of cfCh in TME; 2) Immuno-fluorescence (IF) analysis of intracellular antioxidant enzymes; and 3) IF analysis of 10 hallmarks of cancer represented by 23 biomarkers. Results: 1) FI and Confocal microscopy detected extensive presence of dually fluorescently labelled cfCh particles in TME, which were dramatically reduced following R-Cu treatment. 2) IF analysis detected significantly elevated levels of three intra-cellular anti-oxidant enzymes in post R-Cu samples, suggesting that cells had mounted a defense mechanism to counteract free radicals that had entered into them. No difference between day 0 and day 14 samples was seen in the untreated control group. 3) IF analysis of 23 cancer hallmark biomarkers showed significant down-regulation in the post R-Cu samples, which were most marked in dose levels I and II. No difference between day 0 and day 14 samples was seen in the control group. Conclusion: We show in a human tumor model that cfCh particles released into TME from dying tumor cells activate cancer hallmarks in surviving cells, and that the cfCh inactivating agent R-Cu can significantly down-regulate cancer hallmark levels suggesting its therapeutic potential. Citation Format: Indraneel Mittra, Hitesh Singhavi, Aishwarya Pilankar, Venkat Raghuram Gorantla, Sophiya Siddiqui, Naveen Kumar Khare, Vishalkumar Jadhav, Kavita Pal, Pankaj Chaturvedi. Cell-free chromatin particles released into the microenvironment from dying tumor cells activate cancer hallmarks in surviving cells: a study in advanced squamous cell carcinoma of oral cavity with therapeutic implications [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 2514.

Development of flexible electrochemical impedance spectroscopy-based biosensing platform for rapid screening of SARS-CoV-2 inhibitors

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the cells through the binding of its spike protein (S-protein) to the cell surface-expressing angiotensin-converting enzyme 2 (ACE2). Thus, inhibition of S-protein-ACE2 binding may impede SARS-CoV-2 cell entry and attenuate the progression of Coronavirus disease 2019 (COVID-19). In this study, an electrochemical impedance spectroscopy-based biosensing platform consisting of a recombinant ACE2-coated palladium nano-thin-film electrode as the core sensing element was fabricated for the screening of potential inhibitors against S-protein-ACE2 binding. The platform could detect interference of small analytes against S-protein-ACE2 binding at low analyte concentration and small volume (0.1 μg/mL and ~1 μL, estimated total analyte consumption < 4 pg) within 21 min. Thus, a few potential inhibitors of S-protein-ACE2 binding were identified. This includes (2S,3aS,6aS)-1-((S)–N-((S)-1-Carboxy-3-phenylpropyl)alanyl)tetrahydrocyclopenta[b] pyrrole-2-carboxylic acid (ramiprilat) and (2S,3aS,7aS)-1-[(2S)-2-[[(2S)-1-Carboxybutyl]amino]propanoyl]-2,3,3a,4,5,6,7,7a-octahydroindole-2-carboxylic acid (perindoprilat) that reduced the binding affinity of S-protein to ACE2 by 72% and 67%; and SARS-CoV-2 in vitro infectivity to the ACE2-expressing human oral cavity squamous carcinoma cells (OEC-M1) by 36.4 and 20.1%, respectively, compared to the PBS control. These findings demonstrated the usefulness of the developed biosensing platform for the rapid screening of modulators for S-protein-ACE2 binding.

HPV sensitizes OPSCC cells to cisplatin-induced apoptosis by inhibiting autophagy through E7-mediated degradation of AMBRA1

ABSTRACT Oropharyngeal squamous cell carcinoma (OPSCC) is an increasing world health problem with a more favorable prognosis for patients with human papillomavirus (HPV)-positive tumors compared to those with HPV-negative OPSCC. How HPV confers a less aggressive phenotype, however, remains undefined. We demonstrated that HPV-positive OPSCC cells display reduced macroautophagy/autophagy activity, mediated by the ability of HPV-E7 to interact with AMBRA1, to compete with its binding to BECN1 and to trigger its calpain-dependent degradation. Moreover, we have shown that AMBRA1 downregulation and pharmacological inhibition of autophagy sensitized HPV-negative OPSCC cells to the cytotoxic effects of cisplatin. Importantly, semi-quantitative immunohistochemical analysis in primary OPSCCs confirmed that AMBRA1 expression is reduced in HPV-positive compared to HPV-negative tumors. Collectively, these data identify AMBRA1 as a key target of HPV to impair autophagy and propose the targeting of autophagy as a viable therapeutic strategy to improve treatment response of HPV-negative OPSCC. Abbreviations: AMBRA1: autophagy and beclin 1 regulator 1; CDDP: cisplatin (CDDP); FFPE: formalin-fixed paraffin-embedded (FFPE); HNC: head and neck cancers (HNC); HPV: human papillomavirus (HPV); hrHPV: high risk human papillomavirus (hrHPV); OCSCC: oral cavity squamous carcinomas (OCSSC); OPSCC: oropharyngeal squamous cell carcinoma (OPSCC); OS: overall survival (OS); qPCR: quantitative polymerase chain reaction; RB1: RB transcriptional corepressor 1; ROC: receiver operating characteristic curve (ROC).

PD-L1 targeting high-affinity NK (t-haNK) cells induce direct antitumor effects and target suppressive MDSC populations

BackgroundAlthough immune checkpoint inhibitors have revolutionized cancer treatment, clinical benefit with this class of agents has been limited to a subset of patients. Hence, more effective means to target tumor...

Management of early oral cavity squamous cancers.

Early oral cavity cancers comprise a favorable entity, amenable to clinical staging and single modality treatment. Surgery typically forms the mainstay of treatment and should ideally address both the primary and the neck in all cases. Careful attention must be paid to reconstruction and rehabilitation of such patients. Radical radiotherapy mainly in the form of brachytherapy can achieve excellent disease related and functional outcomes in a carefully chosen subset of patients. Increasingly, a subset of patients is being recognized, who harbor single or multiple adverse features on histopathology and may therefore benefit from escalation of adjuvant therapy. This review discusses the management of early oral cavity squamous carcinomas (Early OSCCs) in detail and highlights the dilemmas and controversies faced in the management of the same.

Worst pattern of invasion - type 4 (WPOI-4) and Lymphocyte host response should be mandatory reporting criteria for oral cavity squamous cell carcinoma: A re-look at the American Joint Committee of Cancer (AJCC) minimum dataset.

A proportion of early-stage node-negative oral squamous carcinoma patients fail despite complete surgical resection. Adjuvant treatment in early oral cancer is controversial and is often individualized based on stage, depth, and margin status. We reviewed various histological markers in pT1/T2N0 cases, resected upfront with elective nodal dissection, with an emphasis on tumor-tissue interface characteristics of the worst pattern of invasion (WPOI), tumor cell nest size (sCNS), budding and lymphocytic host response (LHR), to assess their prognostic significance. Archived blocks of 95 cases were reviewed. Tumor stage, grade, size, depth of invasion, lymphovascular, and perineural invasion, WPOI, LHR, sCNS, and tumor bud (single cells or <5 cell clusters) score were recorded. Prognostic significance was statistically analyzed using SPSS software version 20. Depth of invasion (P = 0.008), WPOI- 4 and 5 (P = 0.033), sCNS (<5 cells) at tumor interface (P = 0.010), high bud count (≥3 buds/40 × hpf) (P = 0.021) and poor LHR (P = 0.019) correlated significantly with poor disease-free survival on univariate analysis. However, on multivariate analysis only LHR and WPOI-4 (that is presence of small cell nests or buds) were significant, with high hazard ratio of 4.351 (95% CI 1.290-14.676, P = 0.018) and 5.019 (95% CI 1.212-20.789, P = 0.026), respectively. We propose mandatory reporting of WPOI-4 at the tumor interface and absence of LHR, as significant markers of poor prognosis in early-stage oral cavity squamous carcinoma.

Psychological characteristics versus swallowing and speech rehabilitation efficiency in patients after oral cavity cancer excision

Personality traits of the patients surgically treated due to oral cancer form anxiety and depression levels associated with body deformation, as well as life quality during illness, and they are also associated with life span of the patients. It is purposeful to take personality traits into account during treatment management and rehabilitation of the patients. The aim of work is to recognize the association between personality traits and functional rehabilitation course in the patients treated due to oral cancer. 100 patients (W – 42, M – 58; 55.78 ±11.68 years) surgically treated due to oral cavity squamous carcinoma. Patients participated in the rehabilitation of oral functions. Wound healing course, postoperative facial deformity, breathing, swallowing, and speech were assessed in relation to “self-image”, “body image”, and “the level of acceptance of the disease” according to the Adjective Check List ACL-37, Body Cathexis Scale, and Illness Acceptance Scale after 2, 4, and 12 weeks post-surgically. Greater swallowing efficiency after 4 weeks post-surgically was present in patients with a stronger need for order and endurance. Patients who achieved greater speech efficiency in the 4th week post-surgically accepted their illness in a greater part. Patients in whom post-surgical deformity was greater showed lesser intensity in: achievements, domination, endurance, self-exposure, spontaneity in interpersonal contacts. These patients are characterized with lower self-reliance and greater need for counselling.

Research on miRNA-195 and target gene CDK6 in oral verrucous carcinoma.

Oral verrucous carcinoma (OVC) is a verrucous variant of oral cavity squamous carcinoma (OSCC). The expression of miRNA from OVC and OSCC including their matched normal oral mucosa tissues was profiled through the Affymetrix GeneChip miRNA Arrays. TargetScan and miRanda databases were used to predict the target gene of miRNA-195. The quantitative real-time PCR was applied to validate the expression of miRNA-195. The expression of CDK6 was investigated by the quantitative real-time PCR and immunohistochemistry. In this study, a total of 23 and 35 differentially expressed miRNAs were identified in OVC and OSCC, respectively. Moreover, 44 miRNAs were differentially expressed between OSCC and OVC. In addition, miRNA-195 was significantly decreased in both OVC and OSCC compared to normal oral mucosa. Target gene prediction demonstrated that CDK6 was a potential target gene of miRNA-195. In the quantitative real-time PCR, miR-195 was decreased in OVC and OSCC, which was consistent with the result of miRNA chip analysis. CDK6 was increased in OVC and OSCC, which was opposite to the expression of miRNA-195. In conclusion, miRNA-195 could be the potential diagnosis biomarker and therapy target of OVC.

Does addition of neck ultrasonography to physical examination, in follow-up of patients with early stage, clinically node negative oral cancers, influence outcome? A randomized control trial (RCT).

6020 Background: We previously reported results of a RCT demonstrating superiority of elective neck dissection (END) over therapeutic neck dissection (TND) in early oral cancer patients with clinically node negative neck1. We now report the results of the second question in this trial –elucidating the role of ultrasonography (USG) during follow-up, based on the hypothesis that addition of imaging would detect neck nodes earlier and improve salvage and survival (NCT00193765). Methods: Patients with lateralized T1 or T2 squamous carcinoma of oral cavity after initial surgery (excision of primary with/without neck dissection) were randomized to follow up with physical examination plus neck ultrasound (PE+USG) performed in a standardized manner versus physical examination (PE). The primary end point was overall survival (OS)1. Results: This report includes results of 500 patients in the same cohort reported earlier1with a median follow up of 39 months; 252 patients were randomized to PE+USG and 244 to PE. Both arms were balanced for stratification factors and surgical procedure (END vs. TND). There were 118 recurrences with 67 deaths in PE+USG and 109 recurrences with 62 deaths in PE, respectively. There was no OS difference between PE+USG and PE in unadjusted analysis (3-year OS 73.3% and 73.8%, respectively, HR = 1.02, 95%CI 0.73-1.45, p = 0.89) and after adjustment (HR = 0.81, 95%CI 0.51-1.29, p = 0.37) for stratification factors, prognostic factors, surgical treatment (END vs. TND) and an interaction term between two study questions, in a Cox model. END vs. TND continued to be highly significant for OS in this model (HR = 0.54, 95%CI 0.32 - 0.92, p = 0.02). Within TND (wait and watch) arm there was no significant difference between PE+USG and PE (3-year OS 67.3% and 67.6% respectively, HR = 0.96, 95%CI 0.62–1.5, p = 0.86). Conclusions: Neck ultrasound confers no survival advantage over physical examination in postoperative follow-up of clinically node negative early stage oral cancer patients. 1. N Engl J Med 2015;373:521-9 Clinical trial information: NCT00193765.

Multiparameter study of the immunophenotype of tumor infiltrating lymphocytes, in cancer patients

For the first time in Russia the immunophenotype of tumor infiltrated lymphocytes (TIL) was investigated with the use of a method of quantitative flow cytometry. Samples from 104 patients, suffering from solid tumors (such as breast cancer, ovarian cancer, melanoma and oral cavity squamous carcinoma), were analyzed in this investigation. In the difference of cytomorphological analysis, the method of flow cytometry identified TIL in 100% of cases. In the structure of CDS+Т- lymphocytes the ratio CD4/CD8 was equal to 1,1±0,1. Serial gating strategy allowed to assess minor subpopulations of regulatory T-lymphocytes CD45+CD4+CD127+low/neg and CD45+CD8+CD28-CD11b-. Regulatory mechanisms with involvement of CD8 T-cells played the main role in the generation of immune responses at the tissue level ofpatients, suffering from solid tumors, independent of nosological form of disease.

Elective versus therapeutic neck dissection in the clinically node negative early oral cancer: A randomised control trial (RCT).

LBA3 Background: Management of the neck in early oral cancers has been a matter of debate with clinical equipoise between elective (END) or therapeutic neck dissection (TND). Methods: This is a prospective phase III RCT (NCT00193765) to test the superiority of END at the time of primary surgery over TND (neck dissection at the time of nodal relapse) in patients with lateralized T1 or T2 squamous carcinoma of oral cavity, amenable to peroral excision. Patients were stratified based on size, site, sex and preoperative neck ultrasound. The primary end point was overall survival (OS) and secondary end point was disease-free survival (DFS). The trial was planned to demonstrate a 10% superiority (1-sided α = 0.05 and β = 0.2) in OS for END vs. TND, assuming 60% 5-year OS in TND arm, with a planned sample size of 710. Results: This trial was terminated after 596 patients were randomized between January 2004 and June 2014. An interim intent-to-treat analysis of initial 500 patients (255 in TND, 245 END) with a minimum follow-up of 9 months was performed as mandated by Data and Safety Monitoring Committee based on the number of observed deaths in each arm. Both arms were balanced for site and stage. There were 427 tongue, 68 buccal mucosa and 5 floor of mouth tumors; 221 were TI and 279 T2. At a median follow-up of 39 months there were 146 recurrences in TND and 81 in END arms respectively. The 3-year OS was significantly higher in END compared to TND arm (80.0% vs. 67.5%, HR = 0.63, 95%CI 0.44-0.89, p = 0.01) as was 3-year DFS (69.5% vs. 45.9%, HR = 0.44, 95%CI 0.34-0.58, p &lt; 0.001). After adjusting for stratification factors in Cox regression, END continued to be significantly superior to TND for both OS and DFS. Conclusions: There were 8 excess deaths for every 15 excess recurrences in the TND arm. Elective neck dissection in patients with early oral SCC results in 37% reduction in mortality and should be considered the standard of care. Clinical trial information: NCT00193765.

Effectiveness of Supraomohyoid Neck Dissection in Oral Cancers with N1 Neck

ABSTRACT Aim Lymph node metastasis in squamous carcinoma of oral cavity carries poor prognosis. Majority of patients in our country present with locally advanced malignancy which has high incidence of micrometastasis. A comprehensive neck dissection in patients with N0 and N1 neck is overkill with resultant morbidity. Lymph node metastasis from oral cavity has predictable pattern. Supraomohyoid neck dissection (SOND) is a one stage treatment and staging procedure in patients with locally advanced oral cancer with N0 and N1 neck. Materials and methods We are presenting a series of 117 patients with malignancy of oral cavity with N1 neck who underwent SOND, majority involved buccal mucosa. Among the 117 patients who were clinical N1 cases, 53 (45.3%) were found to have positive nodes on histopathology and 64 (54.7%) were false. Level I lymph node metastasis (77.3%) was seen in majority of the oral cancers. After mean follow-up of 30 months, 71 patients are alive and disease-free, twelve patients had local and six (5.1%) had nodal recurrences. Conclusion Supraomohyoid neck dissection in locally advanced oral malignancies with N1 neck, carries low morbidity and complications and is effective substitute for modified radical neck dissection in suitable cases. Postoperative radiotherapy improves the outcome. How to cite this article Harshita TR, Mohiyuddin SMA, Sagayaraj A, Suresh TN, Merchant S. Effectiveness of Supraomohyoid Neck Dissection in Oral Cancers with N1 Neck. Int J Head Neck Surg 2015;6(2):73-75.

Tumor infiltrating lymphocytes (TIL) and prognosis in oral cavity squamous carcinoma: A preliminary study

Tumor infiltrating lymphocytes (TILs) in the microenvironment reflect may tumor biology and predict outcome. We previously demonstrated that infiltrates of CD4, CD8, and FoxP3 positive lymphocytes were associated with HPV-status and survival in oropharyngeal cancers. To determine if TILs were of prognostic importance in oral cancer, TIL levels were evaluated retrospectively in 52 oral cancer patients treated with surgery and correlations with outcome determined. Complete TIL and clinical data were available for 39 patients. Levels of CD4, CD8, FoxP3 (Treg), CD68 and NK cells were assessed by immunohistochemistry in tumor cores on a tissue microarray. Associations with clinical variables, tobacco and alcohol use and histologic features were assessed using Spearman correlation coefficient and the non-parametric Kruskal-Wallis testing. Time-to-event outcomes were determined using univariate and multivariate Cox models. Median follow up was 60 months. The ratio of CD4/CD8 (p=.01) and CD8 infiltrates (p=.05) were associated with tumor recurrence but not overall survival. Lower CD4 infiltrates were associated with alcohol use (p=.005) and poor tumor differentiation (p=.02). Interestingly, higher levels of CD68+ macrophages were found associated with positive nodes (p=.06) and poorer overall survival (p=.07). Overall and DSS survival were significantly shorter for patients with positive nodes, extracapsular spread, or perineural invasion. Infiltrating immune cell levels in oral cavity cancer appear influenced by health behaviors and tumor characteristics. In contrast to oropharynx cancer, infiltrates of CD68 positive tumor associated macrophages may contribute to metastatic behavior and outcome in advanced oral cavity carcinoma.

Envisioning the Next WHO Head and Neck Classification

The next WHO classification should abandon "salivary duct carcinoma"; conventional salivary duct carcinoma should be classified as "high-grade salivary duct carcinoma". Low-grade salivary duct carcinoma should replace the current nosology of "low-grade cribriform cystadenocarcinoma". Cystadenocarcinoma should be classified with the descriptor "Not Otherwise Specified" and should be considered an exclusionary diagnostic category. On the other hand, "Not Otherwise Specified" does not fit for hyalinizing clear cell carcinoma (HCCC). The EWSR1-ATF1 fusion is specific for HCCC within the context of salivary neoplasia. We recommend adding "hyalinizing" even though this feature is not present in all cases; the benefit of which is the mental association with a salivary clear cell malignancy. Sinonasal Renal Cell-like Adenocarcinoma (SNRCLA) is a distinct clear cell neoplasm and should be added to the next WHO classification. Future studies will bear out whether SNRCLA is even a low-grade carcinoma, or may be reclassified as "adenoma". Lastly, the next WHO monograph should include the Risk Model in the general introductory statements on oral squamous cell carcinoma, under a subheading of "Histological Prognosticators". The positive predictive value for developing locoregional recurrence in patients with low-stage oral cavity squamous carcinoma (OSCC) and "worst pattern of invasion type-5" (WPOI-5) is 42 %. Low-stage high-risk OSCC with a combination of features other than WPOI-5 is associated with 32 % likelihood for locoregional progression. WPOI-5 also predicts occult metastatic disease (p = 0.0001, Chi squared, 2 DF). Thus the Risk Model can also be used to make decisions regarding staged elective neck dissections.

Clinical Outcomes of Patients with Oral Cavity Squamous Cell Carcinoma and Retropharyngeal Lymph Node Metastasis Identified by FDG PET/CT

PurposeRetropharyngeal lymph node (RPLN) metastasis is an uncommon finding in patients with oral cavity squamous carcinoma (OSCC). We sought to investigate the clinical outcomes, clinicopathological characteristics, and the priority of treatment with curative intent in OSCC patients with RPLN involvement.Methods and MaterialsBetween January 2007 and January 2011, we identified 36 patients with primary RPLN metastases (n = 10) or RPLN relapse (n = 26). The follow-up continued until June 2013. Disease-specific survival (DSS), disease-free survival (DFS), and the potential benefits of salvage therapy served as the main outcome measures.ResultsThe 2-year DSS and DFS rates of untreated patients with RPLN involvement were 20% and 24%, respectively. Level IV/V neck lymph node involvement was an adverse prognostic factor for DSS (P = 0.048) and DFS (P = 0.018). All of the patients presenting with neck lymph node involvement at level IV/V died within 6 months. Among patients who were treated for RPLN relapse, the 2-year DSS and DFS rates from the relapse day were 12.8% and 9.6%, respectively. Concomitant contralateral neck lymph node metastases (N2c) were associated with lower 2-year DSS (P = 0.005) and DFS (P = 0.011) rates. Moreover, five (55%) of the nine patients with recurrent disease in the contralateral RPLN had distant metastases within 6 months. Salvage therapy yielded the maximum survival benefit in patients without N2c disease and ipsilateral RPLN involvement alone (P = 0.005).ConclusionOSCC patients with RPLN involvement have poor outcomes. The risk factor for definitive treatment in OSCC patients with FDG PET/CT defined RPLN disease in primary disease was neck lymph node involvement at level IV/V and N2c and/or contralateral RPLN disease in recurrent disease. Treatment efforts with curative intent should be tailored according to individual risk factors.

LIHNCS trial: Lugol's iodine in head and neck cancer surgery.

e16042 Background: Residual dysplasia at margins of mucosal tumour resection is a cause of disease failure. While risk of transformation of dysplasia is difficult to assess, malignant cells within a field of dysplastic change indicate high transformation potential of this dysplastic field. Lugol's iodine assists in the assessment of surgical margins at tumour resection to ensure removal of margin dysplasia where present and resectable using the surrogate biomarker of glycogen storage. This multicenter RCT assesses efficacy of this technique in head and neck cancer surgery and is recruiting over the next two years. Methods: Patients undergoing primary surgery for oral cavity and oropharynx squamous carcinoma are randomised to gold standard surgical resection or to resection guided by Lugol's iodine application. Mucosal surfaces are irrigated with saline, carbocisteine solution applied to remove surface mucus and then irrigated with Lugol's iodine solution. Where present, adjacent visible surface dyplasia is resected with the tumour specimen. Histopathologists are blinded to the technique used. Histopathology is repeated centrally for quality control. Margin status is assessed for involved, close and clear for carcinoma and for presence of dysplasia at margins. Quality of life data are collected at baseline, six weeks, six, twelve and 24 months. Results: Our cohort study of 100 cases showed a reduction in margin dyplasia from 32% to 4% p&lt;0.001. A feasibility pilot trial recruited 98 patients with 100% consent and data collection rates. Recruitment is progressing on schedule and at time of writing two sites are open. Forty six patients have consented in four sites and are included in the trial to date. A further 12 sites are in the trial set up process. We will report our interim data regarding sites open, screened and consented rates and outcomes so far. Conclusions: To date recruitment is on schedule. We have demonstrated the acceptability of the trial and techniques therein to both patients and surgeons. This is a promising technique which may modify head and neck cancer surgery by targeting dysplasia for inclusion at time of resection of primary cancer. Thus locoregional recurrence may be reduced in a proportion of patients undergoing curative surgical resection.

Oral Cavity Squamous Carcinoma; Effects of Primary Site on Survival

Oral Cavity Squamous Carcinoma; Effects of Primary Site on Survival

Non–Cancer-Related Deaths From Suicide, Cardiovascular Disease, and Pneumonia in Patients With Oral Cavity and Oropharyngeal Squamous Carcinoma

To study non-cancer-related mortality rates over time and examine the possible causes for several major deaths in patients with oral cavity and oropharyngeal (OC/OP) cancer. Retrospective cohort analysis using the Surveillance, Epidemiology, and End Results (SEER) cancer registry data of the National Cancer Institute. Cause-specific mortality rates during the first year after diagnosis of OC/OP cancer were calculated for 4 cohorts (1980-1984, 1990-1994, 2000-2003, and 2004-2007). The percentage changes over time were calculated. Standardized mortality ratios (SMRs) for suicide, cardiovascular disease, and pneumonia were calculated and compared with patient demographic and clinical characteristics. We analyzed data for 32,487 patients in 4 cohorts. From 1980-1984 to 2004-2007, mortality from suicide increased by 406.2% (P = .01), cardiovascular disease-related and pneumonia-related mortality decreased by 45.9% (P < .001) and 42.9% (P = .009), respectively, and rates of other non-cancer-related deaths did not change. Compared with the general population, patients diagnosed as having OC/OP cancer were at a significantly higher risk of mortality from suicide (SMR, 7.8; 95% CI, 4.6-12.4; P < .001), cardiovascular disease (SMR, 2.4; 95% CI, 2.1-2.7; P < .001), and pneumonia (SMR, 8.9; 95% CI, 6.8-11.5; P < .001) during the first year after cancer diagnosis. Risk factors for increased mortality included age of 55 to 64 years, marital status (including never married, divorced, or separated), advanced tumor stage (including regional and distant disease), treatment with radiotherapy alone, and pharyngeal tumor location. Suicide rates have significantly increased in patients with OC/OP cancer since 1980 to 1984. Although cardiovascular disease-and pneumonia-related deaths have significantly decreased over time, they remain higher than the general US population. Increased knowledge of risk factors associated with non-cancer-related mortality in OC/OP cancer may lead to early intervention and enhanced overall survival.