Optimising Patient Outcomes in Tongue Cancer: A Multidisciplinary Approach.

A multidisciplinary approach to the management of tongue cancer is vital for achieving optimal patient outcomes. Nursing and allied health professionals play essential roles within the team. We developed symposia comprising a series of online lectures offering a detailed perspective on the role each discipline and consumer perspective has in the management of patients with tongue cancer. The topics, including epidemiology and prevention, diagnosis, treatment planning, surgery, adjuvant care, and the management of recurrent or metastatic disease, were thoroughly examined. The symposia highlighted the significance of fostering collaboration and continuous learning through a multidisciplinary approach. This initiative should be relevant to healthcare professionals, researchers, and policymakers striving to enhance patient outcomes in tongue cancer care through innovative collaboration.

Head and neck mucoepidermoid carcinoma: does AFIP histological grading correlate with rate of nodal metastases?

OBJECTIVE: The aim of this study is to retrospectively evaluate the presentation of head and neck mucoepidermoid carcinoma at the Royal Melbourne Hospital and identify the significance of AFIP histological grading on the risk of neck metastasis and cancer free survival. MATERIALS AND METHODS: This study is a retrospective cohort analysis of patients treated for head and neck mucoepidermoid carcinoma at the RMH between 2005 and 2022. Patient demographics, treatment, pathology, in particular the AFIP histological grading of the primary tumour, and outcomes were collected and tabulated. Time to recurrence was recorded, and survival outcomes were calculated with Kaplan-Meier method. Comparisons were made on different histological grading and regional metastases. RESULTS: Thirty-three patients were identified and thirty met the inclusion criteria. There was an age range of 18-77 years (median 54 years) with no significant sex difference. Our patients had a 94% 5-year survival and an 86% 10-year survival. Thirteen patients had elective neck dissection and 2 out of 13 (15%) of the patients had positive neck disease. Of the two patients with regional metastasis, the primary tumour was graded as intermediate and low grade. No high-grade MEC patients had regional metastasis. CONCLUSION: Mucoepidermoid carcinoma of the head and neck is associated with a good disease-specific and overall survival despite the presence of regional metastasis. The AFIP histological grading system did not have a statistically significant correlation to the incidence of nodal metastasis.

Evaluation of the validity and screening performance of a revised single-item fear of cancer recurrence screening measure (FCR-1r).

OBJECTIVE: Fear of cancer recurrence (FCR) is highly prevalent among cancer survivors, but irregularly identified in practice. Single-item FCR measures suitable for integration into broader psychosocial screening are needed. This study evaluated the validity of a revised version of the original FCR-1 (FCR-1r) and screening performance alongside the Edmonton Symptom Assessment System - Revised (ESAS-r) anxiety item. METHODS: The FCR-1r was adapted from the FCR-1 and modelled on the ESAS-r. Associations between FCR-1r and FCR Inventory-Short Form (FCRI-SF) scores determined concurrent validity. Relationships of FCR-1r scores with variables related (e.g., anxiety, intrusive thoughts) and unrelated (e.g., employment/marital status) to FCR determined convergent and divergent validity respectively. A Receiver-Operating Characteristic analysis examined screening performance and cut-offs for the FCR-1r and ESAS-r anxiety item. RESULTS: 107 participants were recruited in two studies (Study 1, July-October 2021, n = 54; Study 2: November 2021-May 2022, n = 53). The FCR-1r demonstrated concurrent validity against the FCRI-SF (r = 0.83, p < 0.0001) and convergent validity versus the Generalised Anxiety Disorder-7 (r = 0.63, p < 0.0001) and Impact of Event Scale-Revised Intrusion subscale (r = 0.55, p < 0.0001). It did not correlate with unrelated variables (e.g., employment/marital status), indicating divergent validity. An FCR-1r cut-off ≥5/10 had 95% sensitivity and 77% specificity for detecting clinical FCR (area under the curve (AUC) = 0.91, 95% CI 0.85-0.97, p < 0.0001); ESAS-r anxiety cut-off ≥4 had 91% sensitivity and 82% specificity (AUC = 0.87, 95% CI 0.77-0.98, p < 0.0001). CONCLUSIONS: The FCR-1r is a valid and accurate tool for FCR screening. Further evaluation of the screening performance of the FCR-1r versus the ESAS-r anxiety item in routine care is needed.

Study protocol for the evaluation of Fear-Less: a stepped-care program for fear of cancer recurrence in survivors with early-stage disease.

BACKGROUND: Fear of cancer recurrence (FCR) is a significant unmet need amongst cancer survivors and is consistently associated with psychological distress and impaired quality of life. Psychological interventions for FCR, such as ConquerFear, have demonstrated efficacy in reducing FCR and improving emotional wellbeing. Unfortunately, there are barriers to the uptake of evidence-based FCR treatments in clinical practice. A stepped-care FCR treatment model may overcome these barriers and has demonstrated potential in people with advanced melanoma. This study aims to evaluate the acceptability, feasibility, and impact of a stepped-care FCR treatment model (Fear-Less) in people with other cancer types, who have completed treatment with curative intent. METHODS: Sixty people with early-stage cancer (defined as individuals who have received treatment with curative intent and with no metastatic disease) will be screened for FCR using the Fear of Cancer Recurrence Inventory-Short Form (FCRI-SF). Individuals reporting moderate FCR (FCRI-SF between 13 and 21) will be offered a clinician-guided self-management resource; those reporting high FCR (FCRI-SF ≥ 22) will be offered individual therapy according to the ConquerFear protocol. Participants will complete purpose-built evaluation surveys assessing their FCR screening and intervention experiences. Clinicians will also complete a survey regarding their experiences of the treatment model. Fear-Less will be evaluated in terms of (1) acceptability (i.e., patient and clinician experience), (2) feasibility (i.e., referral uptake, treatment adherence, and time taken to screen and deliver interventions), and (3) impact (i.e., pre- to post-intervention FCR changes). DISCUSSION: The Fear-Less stepped-care model is a novel framework for screening FCR and stratifying survivors to the appropriate level of treatment. Our study will provide an indication of whether Fear-Less is a feasible and acceptable FCR model of care amongst survivors with early-stage disease and inform further investigations of this model. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR); ACTRN12622000818730 .

Genomic Signature of Oral Squamous Cell Carcinomas from Non-Smoking Non-Drinking Patients.

Molecular alterations in 176 patients with oral squamous cell carcinomas (OSCC) were evaluated to delineate differences in non-smoking non-drinking (NSND) patients. Somatic mutations and DNA copy number variations (CNVs) in a 68-gene panel and human papilloma virus (HPV) status were interrogated using targeted next-generation sequencing. In the entire cohort, TP53 (60%) and CDKN2A (24%) were most frequently mutated, and the most common CNVs were EGFR amplifications (9%) and deletions of BRCA2 (5%) and CDKN2A (4%). Significant associations were found for TP53 mutation and nodal disease, lymphovascular invasion and extracapsular spread, CDKN2A mutation or deletion with advanced tumour stage, and EGFR amplification with perineural invasion and extracapsular spread. PIK3CA mutation, CDKN2A deletion, and EGFR amplification were associated with worse survival in univariate analyses (p < 0.05 for all comparisons). There were 59 NSND patients who tended to be female and older than patients who smoke and/or drink, and showed enrichment of CDKN2A mutations, EGFR amplifications, and BRCA2 deletions (p < 0.05 for all comparisons), with a younger subset showing higher mutation burden. HPV was detected in three OSCC patients and not associated with smoking and drinking habits. NSND OSCC exhibits distinct genomic profiles and further exploration to elucidate the molecular aetiology in these patients is warranted.

Contralateral neck failure in oral tongue cancer: Outcomes from two centers using predefined treatment criteria.

BACKGROUND: The objective was to determine the incidence of, and factors associated with contralateral neck failure (CNF) in oral tongue squamous cell carcinoma (OTSCC). METHODS: Consecutive patients with OTSCC between 2007 and 2016 were included. The predefined policy of the contralateral neck included neck dissection (ND) where the primary tumor extended/crossed midline or the contralateral neck was involved; and elective nodal irradiation (ENI) where the primary tumor was ≤1 cm from midline/2 cm from tip. RESULTS: This study included 258 patients. ND was ipsilateral 169 (66%) and bilateral 33 (13%). Fifty-five patients (21%) received ENI to the undissected contralateral neck. CNF occurred in 19 patients (7%) and was similar by treatment received. Utilizing this approach, we observed higher rates of CNF with increasing N classification, perineural invasion, extracapsular extension, and depth of invasion ≥6 mm. CONCLUSIONS: Using our institutional policy of treatment to the contralateral neck, a low rate of CNF (≤10%) was observed.

Impact of histological Oral Tongue Cancer margins on locoregional recurrence: A multi-centre retrospective analysis.

OBJECTIVES: To assess the effect of the histological margins (HM) upon locoregional failure (LRF) and overall survival (OS) for oral tongue squamous cell carcinoma (OTSCC). MATERIALS AND METHODS: We undertook a retrospective review of 258 patients, across two institutions, treated for OTSCC between 2007 and 2016. A Cox-proportional hazards model was used to compare the relative hazard ratio of HM to the accepted standard of 5 mm margins for LRF and OS. RESULTS: The median follow up period was 4.8 years. The 5 year OS and freedom from LRF were 69% and 75% respectively. The Cox-proportional hazards model adjusted for age, DOI and LVI showed increasing risk of mortality and LRF with decreasing HM widths of <5 mm. CONCLUSION: HM >5 mm were associated with a risk reduction of both LRF and mortality in OTSCC. This study supports >5 mm HM being the oncologic goal of surgery.

Common benign and malignant oral mucosal disease.

BACKGROUND: Mucosal diseases of the oral cavity are relatively common, and patients often seek initial assessment from their general practitioner. OBJECTIVE: The aim of this article is to provide an overview of common oral mucosal diseases to help with formulating a differential diagnosis and stratifying the urgency of referral. DISCUSSION: Pathological mucosal conditions of the oral cavity and jaws commonly present as a mucosal ulcer or a white, red or pigmented lesion. In this review, the authors outline the most common conditions organised according to their clinical presentation and describe their typical appearance and management.

Common causes of 'swelling' in the oral cavity.

BACKGROUND: Conditions that present as a 'swelling' in the oral cavity are relatively common, and patients may seek initial assessment from their general practitioners. OBJECTIVE: The aim of this article is to provide an overview of common causes of a 'swelling' in the oral cavity to help with formulating a differential diagnosis and stratifying the urgency of referral. DISCUSSION: Pathological conditions in the oral cavity (excluding mucosal presentations) may present as a swelling in the submucosa or jaws, symptoms related to teeth and/or gums or an incidental finding on imaging. In this review, the authors outline the most common submucosal or jaw swellings, organised according to their clinical presentations, and describe their typical appearance and management.

Relationship between age, comorbidities and complications in head and neck cancer patients undergoing curative surgery.

BACKGROUND: Both age and comorbidity are accepted as significant prognostic factors for adverse perioperative outcomes in major surgery. Elderly patients may be overlooked for radical treatment for fear of poor perioperative outcome. We aim to assess the relationship between age, comorbidities and post-operative outcomes in a tertiary head and neck unit. METHODS: A retrospective analysis was undertaken on 651 patients who underwent surgery for head and neck cancer at a tertiary hospital between 2007 and 2014. RESULTS: A total of 253 (38.9%) patients were aged ≥70 years and 398 (61.1%) patients were ≤69 years. Age alone did not predict prolonged post-operative stay, perioperative complications nor perioperative mortality. Congestive cardiac failure and/or complicated diabetes were significantly associated with poor outcomes, as was male sex. CONCLUSION: Patients of any age with cardiac failure or complicated diabetes have a higher rate of post-operative complications in head and neck surgery.

Non-smoking, non-drinking elderly females, a 5 year follow-up of a clinically distinct cohort of oral squamous cell carcinoma patients.

To examine differences in survival and clinical outcomes of elderly patients without traditional risk factors presenting with oral squamous cell carcinoma. Retrospective review of 287 consecutive patients divided into 2 treatment period cohorts treated for oral SCC between the 1st Jan 2007 and 31st Dec 2012. Patients were classified as either smoker-drinkers (SD) or non-smoking, non-drinking (NSND). Only patients with oral sub-site primaries according to ICD-10 were included. Carcinomas of the lip, tonsil, base of tongue and oro-pharyngeal subsites were excluded. Of the study population (N = 287), 24.4% were NSND and 9.75% were NSND elderly (older than 70 years) females. >50% of tumours arose from the oral tongue in NSND patients (p = 0.022) and there was a higher rate of recurrent and persistent disease (42.9% vs 27.6%, p = 0.005). Disease specific survival at 5 years was significantly reduced when NSND elderly females were compared to all other patients (p < 0.001) as well as age matched controls (p = 0.006). This effect was verified independently in each cohort.The results of this study suggest that NSND elderly females are a distinct patient population with poorer disease specific survival outcomes.

The role of human papillomavirus in p16-positive oral cancers.

BACKGROUND: The aim of this study was to identify the presence and frequency of human papillomavirus (HPV) nucleic acid in p16-positive oral squamous cell carcinomas (OSCCs), to assess whether the virus was transcriptionally active and to assess the utility of p16 overexpression as a surrogate marker for HPV in OSCC. METHODS: Forty-six OSCC patients treated between 2007 and 2011 with available formalin-fixed paraffin-embedded (FFPE) specimens were included. Twenty-three patients were positive for p16 by immunohistochemistry (IHC) and these were matched with 23 patients with p16-negative tumours. Laser capture microdissection of the FFPE OSCC tissues was undertaken to isolate invasive tumour tissue. DNA was extracted and tested for high-risk HPV types using a PCR-ELISA method based on the L1 SPF10 consensus primers, and a real-time PCR method targeting HPV-16 and HPV-18 E6 region. Genotyping of HPV-positive cases was performed using a reverse line blot hybridization assay (Inno-LiPA). RNAScope® (a chromogenic RNA in situ hybridization assay) was utilized to detect E6/E7 mRNA of known high-risk HPV types for detection of transcriptionally active virus. RESULTS: HPV DNA was found in 3 OSCC cases, all of which were p16 IHC-positive. Two cases were genotyped as HPV-16 and one as HPV-33. Only one of the HPV-16 cases was confirmed to harbour transcriptionally active virus via HPV RNA ISH. CONCLUSION: We have shown that the presence of transcriptionally active HPV rarely occurs in OSCC and that p16 is not an appropriate surrogate marker for HPV in OSCC cases. We propose that non-viral mechanisms are responsible for the majority of IHC p16 overexpression in OSCC.

Survival Outcomes of Mucosal Melanoma in the Head and Neck: Case Series and Review of Current Treatment Guidelines.

PURPOSE: Malignant mucosal melanoma of the head and neck (MMHN) is an aggressive and rare neoplasm with poor long-term outcomes. The aim of this study is to evaluate the outcomes of patients treated by a single-institution head and neck multidisciplinary team. MATERIALS AND METHODS: In this retrospective case series, all MMHN cases treated at the Royal Melbourne Hospital from 1990-2015 were retrospectively reviewed. Patient demographic characteristics (eg, age), treatment offered, pathology, and outcomes were collected, tabulated, and correlated with outcomes. Survival outcomes were calculated by the Kaplan-Meier method. Comparison was made between oral and sinonasal melanomas. RESULTS: A total of 16 cases were identified. Two were excluded because of inaccessible data. Of the 14 remaining cases, 8 were sinonasal melanomas and 6 were oral cavity melanomas. Sinonasal tumor patients presented with epistaxis or visual impairment. Oral melanoma patients presented with pigmented lesions or ulceration. Follow-up ranged from 4 months to 11 years. In 2 patients, locoregional recurrences developed that were successfully re-excised. Six patients died of distant metastases despite clear surgical margins. Two patients with sinonasal melanomas died of extensive local disease with intracranial invasion. One patient died 4 years after diagnosis without disease. There were no failures in the neck. The 2- and 5-year overall survival rates were 63.3% and 31.7%, respectively, by the Kaplan-Meier method. The difference in survival between oral and sinonasal melanomas was not statistically significant. CONCLUSIONS: Despite clear surgical margins, MMHN has a poor prognosis and most deaths are due to distant metastases. Systemic therapies such as those used in cutaneous melanoma treatment might be used in the future for MMHN.

The SECONDI MAPZ(©) system: new approach for the classification of oncological defects of the midface.

The appearance and function of the midface are crucial physiologically, psychologically, and aesthetically, and defects in the region can be devastating. Most of these defects are caused by operations for cancer, for which surgical access and rehabilitation can be challenging. Clinical evidence in midfacial ablative surgery is limited because differences between existing classifications do not allow a uniform approach to data recording, which makes comparison difficult. We explore the history of the classification of midfacial and maxillary defects, we analyse the shortcomings of those currently in use, and propose a new system that enables defects to be mapped simply, logically, and accurately.

Oral Candida colonization in oral cancer patients and its relationship with traditional risk factors of oral cancer: a matched case-control study.

OBJECTIVES: Candida, an opportunistic fungal pathogen, has been implicated in oral and oesophageal cancers. This study aimed to examine oral Candida carriage in 52 oral cancer patients and 104 age-, gender- and denture status-matched oral cancer-free subjects. MATERIAL AND METHODS: We assessed general health, smoking and alcohol drinking habits, use of alcohol-containing mouthwash and periodontal status (community periodontal index of treatment needs). Yeasts were isolated using oral rinse technique and genetically identified via Real-Time PCR-High resolution melting curve analysis of conserved ribosomal DNA. Conditional and binary logistic regressions were used to identify explanatory variables that are risk factors for oral cancer. RESULTS AND CONCLUSION: The frequencies of oral yeasts' presence and high oral colonization were significantly higher in oral cancer than non-oral cancer patients (p=001; p=0.033, respectively). No significant difference in the isolation profile of Candida species was found between the two groups, except C. parapsilosis was more frequent in non-oral cancer group. Differences were noticed in the incidence of C. albicans strains where significantly more C. albicans genotype-A was isolated from cancer patients and significantly more C. albicans genotype-B isolated from non-cancer patients. Multiple regression analyses showed significant association with cancer observed for alcohol drinking (OR=4.253; 95% CI=1.351, 13.386), Candida presence (OR=3.242; 95% CI=1.505, 6.984) and high oral colonization (OR=3.587; 95% CI=1.153, 11.162). These results indicate that there is a significant association between oral cancer occurrence and Candida oral colonization and that the observed genotypic diversity of C. albicans strains may play a role in oral carcinogenesis.

Differential mechanisms of CDKN2A (p16) alteration in oral tongue squamous cell carcinomas and correlation with patient outcome.

CDKN2A (p16) disruption is reported as a frequent event in head and neck squamous cell carcinomas that confers poor prognosis. We investigated the frequency of different potential mechanisms of CDKN2A inactivation in oral tongue squamous cell carcinomas (OTSCC) and their impact on patient outcome. From a cohort of 153 OTSCC patients, 131 formalin fixed paraffin embedded blocks of pre-treatment primary tumours were suitable for further molecular analysis. We assessed CDKN2A (p16) levels by immunohistochemistry (IHC), promoter methylation status by methylation-sensitive high resolution melting, mutation status by Sanger sequencing, gene copy number variation by fluorescence in situ hybridisation, and correlated these with patient outcome. We found that the majority of OTSCC did not overexpress p16 (110/116, 95%), assessed by IHC. The frequency of CDKN2A mutations was 20% (21/103), homozygous loss was 7% (7/97), hemizygous loss 31% (30/97), and promoter methylation was 18% (20/113). We found no evidence of these mechanisms in 24/106 (23%) p16 IHC negative tumours. No significant correlation was identified between any potential mechanism of CDKN2A inactivation and clinical features, including smoking status and age. There was a non-significant trend for worse overall survival for p16 IHC negative patients versus positive patients (HR = 1.81, 95% CI = 0.44-7.47, p = 0.40). No relationship was found between mechanisms of CDKN2A disruption and patient outcome. In conclusion, we demonstrate that CDKN2A alteration is a frequent event in OTSCC tumourigenesis. However, no correlation was identified between different potential mechanisms of CDKN2A disruption and clinical characteristics or patient outcome.

Quantitative methodology is critical for assessing DNA methylation and impacts on correlation with patient outcome.

BACKGROUND: DNA hypermethylation is reported as a frequent event and prognostic marker in head and neck squamous cell carcinomas (HNSCC). Methylation has been commonly assessed with non-quantitative methodologies, such as methylation-specific PCR (MSP). We investigated previously reported hypermethylated genes with quantitative methodology in oral tongue squamous cell carcinomas (OTSCC). RESULTS: The methylation status of 12 genes in 115 OTSCC samples was assessed by one or more of three quantitative analyses: methylation sensitive high resolution melting (MS-HRM), sensitive-melting analysis after real time-methylation specific PCR (SMART-MSP), and bisulfite pyrosequencing. In contrast to much of the literature, either no or infrequent locus-specific methylation was identified by MS-HRM for DAPK1, RASSF1A, MGMT, MLH1, APC, CDH1, CDH13, BRCA1, ERCC1, and ATM. The most frequently methylated loci were RUNX3 (18/108 methylated) and ABO (22/107 methylated). Interrogation of the Cancer Genome Atlas (TCGA) HNSCC cohort confirmed the frequency of significant methylation for the loci investigated. Heterogeneous methylation of RUNX3 (18/108) and ABO (22/107) detected by MS-HRM, conferred significantly worse survival (P = 0.01, and P = 0.03). However, following quantification of methylation levels using pyrosequencing, only four tumors had significant quantities (>15%) of RUNX3 methylation which correlated with a worse patient outcome (P <0.001), while the prognostic significance of ABO hypermethylation was lost. RUNX3 methylation was not prognostic for the TCGA cohort (P = 0.76). CONCLUSIONS: We demonstrated the critical need for quantification of methylation levels and its impact on correlative analyses. In OTSCC, we found little evidence of significant or frequent hypermethylation of many loci reported to be commonly methylated. It is likely that previous reports have overestimated the frequency of significant methylation events as a consequence of the use of non-quantitative methodology.

Frequency of fibroblast growth factor receptor 1 gene amplification in oral tongue squamous cell carcinomas and associations with clinical features and patient outcome.

OBJECTIVES: Novel therapies are required for patients with recurrent or metastatic oral tongue squamous cell carcinoma (OTSCC). Fibroblast Growth Factor Receptor 1 (FGFR1) amplification frequently occurs in squamous cell carcinoma of the lung and represents a novel druggable therapeutic target in this and other malignancies. This study examined the frequency and clinical associations of FGFR1 amplification in OTSCC. MATERIALS AND METHODS: The frequency of FGFR1 amplification determined by fluorescence in situ hybridization was evaluated in a cohort of 123 OTSCC patients. Associations of FGFR1 amplification with clinical characteristics and outcome were determined. RESULTS: FGFR1 gene amplification was present in 9.3% (10/107) of cases and was significantly associated with smoking status (P = 0.03). FGFR1 amplification was seen more commonly in males (9/10 amplified cases male, P = 0.16) and there were no associations with age, stage, T stage, nodal status, alcohol history or performance status (all P>0.05). Outcome was not significantly different between FGFR1 amplified and non-amplified patients. CONCLUSIONS: Copy number variations of the FGFR1 gene occur in a subset of OTSCC with approximately 10% of cases showing amplification of the gene. FGFR1 amplification may represent a therapeutic target in OTSCC.

Outcomes of patients with maxillofacial osteosarcoma: a review of 15 cases.

PURPOSE: To assess clinical behavior, response to treatment, and factors affecting survival in maxillofacial osteosarcoma treated at a tertiary referral center. PATIENTS AND METHODS: Ethics-approved retrospective review of clinical and pathological records was undertaken for 15 patients managed by the Royal Melbourne Hospital Head and Neck Oncology Tumor Stream. RESULTS: Treatment was a combination of surgery and chemotherapy. Chemotherapy was given as adjuvant, neoadjuvant, or in combination. The overall 2-, 5-, and 15-year disease-free survival rates in this study were 92%, 74%, and 74%, respectively. Using Kaplan-Meier analysis with log rank tests, increasing T stage (P = .01) and positive margins (P = .003) were found to affect survival significantly. Neoadjuvant chemotherapy was not significantly associated with tumor necrosis or improved survival. CONCLUSIONS: Tumor size and adequacy of local control were found to be the most important predictors of outcome.