Jonathan R Clark

Sydney Head and Neck Cancer Institute, Lifehouse at RPA · Head and Neck Surgery

Understanding the barriers and facilitators for prophylactic swallowing and trismus exercises for patients undergoing radiation to the head and neck may help exercise adherence. The analysis reviews all published reports of exercise adherence with a critical appraisal following PRISMA guidelines. A total of 137 potential papers were identified; 20...

Background Head and neck cancer treatment often leads to trismus, a condition characterized by limited mouth opening. Exercise‐based therapy is the most common intervention but there are no clear guidelines as to the optimal exercise regimen. Restorabite™ is a portable and force‐regulated trismus device designed to enhance exercise adherence. This...

Patients treated for oral cancer, may experience restricted mouth opening (trismus). Barriers such as cost have limited the utilization of traditional jaw stretching devices, and consequently, patients experience problems with swallowing, oral care, communication, and cancer surveillance. The safety and efficacy of Restorabite™, a new device design...

Trismus commonly arises after surgery for head and neck cancer (HNC) and its severity is potentiated by postoperative radiotherapy. While the benefit of trismus rehabilitation after surgery and radiotherapy is well established, the evidence during radiotherapy is less clear. This may be due to poor adherence to trismus exercises secondary to acute...

Background For oral cavity squamous cell carcinoma (OSCC), extent of extranodal extension (ENE) (minor, ≤2 mm; major, >2 mm) is differentially prognostic, whereas limitations exist with the 8th edition of American Joint Committee on Cancer/International Union Against Cancer TNM N‐classification (TNM‐8‐N). Methods Resected OSCC patients at four cen...

**Background**: Facial nerve palsy (FNP) leads to a combination of aesthetic and functional deficits with profound psychosocial consequences. Significant advances have been made in restoring dynamic function through a range of facial reanimation solutions. Patient-reported severity scales are predetermined metrics that provide limited insight into...

Background: Perineural spread (PNS) of head and neck cutaneous squamous cell carcinoma (HNcSCC) is a unique diagnostic challenge, presenting with insidious trigeminal (CN V) or facial nerve (CN VII) neuropathies without clinically discernible primary masses. These patients are often sub-optimally investigated and misdiagnosed as Bell's palsy or tr...

Adenoid cystic carcinoma (ACC) is one of the most common primary salivary gland cancers. ACC has several benign and malignant mimics amongst salivary gland neoplasms. An accurate diagnosis of ACC is essential for optimal management of the patients and their follow-up. Upregulation of MYB has been described in 85-90% of ACC, but not in other salivar...

Objective: To evaluate whether prolonged operative time is negatively associated with post-operative complications and length of stay in patients undergoing microvascular free flap reconstruction for complex head and neck defects. Methods: 342 consecutive patients undergoing microvascular reconstruction for head and neck defects between 2017-201...

Purpose: Following transoral robotic surgery (TORS) for oropharyngeal carcinoma (OPC), velopharyngeal incompetence (VPI) is a known consequence that may contribute to swallowing and speech disorders. As the incidence of OPC increases affecting a younger demographic, a better understanding of VPI is required to support speech and swallowing rehabili...

e21577 Background: Response rates to PD1 inhibitors are high in unresectable locally advanced or metastatic cSCC. However, the management of cSCC patients with LN-PNI is challenging given that standard measures of disease burden and treatment response are poorly suited to PNI. This study aims to quantify radiological and symptomatic PD1 inhibitor r...

Introduction: Head and neck angiosarcoma (HN-AS) is a rare and aggressive, representing <1% of all head and neck malignancies. It is characterized by a high rate of local recurrence and poor 5-year survival (10-54%). Australian data in this rare disease is lacking. We aim review the clinical outcomes of HN-AS from two high volume head and neck can...

Oral epithelial dysplasia (OED) represents a spectrum of histologic changes in the oral cavity mucosa that has the potential to transform into oral squamous cell carcinoma. Predicting the risk of malignant transformation is predominantly based on clinicopathologic correlation, histologic examination and grading. OED often poses a diagnostic challen...

Background/objectives: To describe the incidence of primary cutaneous squamous cell carcinoma in coastal NSW Australia. Methods: The design is a case-controlled study of reported cSCC from 2016 to 2019 within a defined region of coastal southern NSW. Participants include all reported pathological diagnoses of cSCC in patients greater than 20 yea...

Background Perinueral invasion (PNI) is recognized as an independent adverse prognostic factor associated with shorter disease free and disease specific survival in a range of malignancies. However, not all histologically detected PNI demonstrate aggressive biologic behaviour. Herein, we systematically review the literature to identify neurotrophic...

Background The relationship between swallowing outcomes and radiotherapy dose to dysphagia and aspiration-related structures (DARS) may be different following definitive versus postoperative radiotherapy (PORT) for mucosal head and neck cancer (HNC) and has not been well-studied. Method Patient- and clinician-reported swallowing measures were pros...

Background In response to the pathophysiology and expected trajectory of dysphagia that arises following treatment for head and neck cancer (HNC), an intensive and progressive approach to dysphagia is warranted. This pilot study evaluates the recovery of swallowing function following the implementation of an exercise-based approach to dysphagia reh...

Purpose: Transoral robotic surgery (TORS) is most commonly undertaken as a minimally invasive approach for early staged oropharyngeal cancers (OPC), with good expectations for a functional recovery. A small number of patients, however, require TORS for recurrent or advanced OPC tumours. Their prospects for longer term recovery of communication and...

Background In developing countries, oral squamous cell carcinoma (OSCC) is predominantly a cancer affecting older males who smoke tobacco. In countries with effective public health strategies, smoking rates are declining rapidly. It is not clear if patients who develop OSCC without these traditional risk factors represent a clinically distinct coho...

Background: We aimed to compare the predictive performance of pN-categories in oral squamous cell carcinoma (OSCC) encompassing the most recent 8th edition (TNM8), its predecessor (TNM7), and a newly proposed algorithm (pN-N+), which classifies patients according to the number of positive lymph nodes and extranodal extension. Methods: Consecutive,...

Background Head and neck surgeons are moving away from routine tracheostomy in free‐flap reconstruction. We reviewed prophylactic tracheostomy use in patients undergoing oral cavity or oropharynx free‐flap reconstruction to identify patient groups who avoided tracheostomy. Secondary aims were to describe complications associated with and without tr...

Background Microvascular free‐flap reconstruction of the head and neck is a common technique utilized across many ages. The purpose of this study was to identify if advanced age or comorbidity was associated with worse post‐operative outcomes in patients undergoing free‐flap reconstruction. Methods A retrospective analysis was performed on 344 con...

Background Heterogeneity within studies examining transoral robotic surgery (TORS) for oropharyngeal cancer (OPC) has made it challenging to make clear conclusions on functional outcomes. Infrequent use of instrumental swallow examinations compounds uncertainty surrounding the proposed functional advantage to TORS. Methods A prospective cohort of...

Objectives The AJCC 8th edition (AJCC 8) has introduced depth of invasion (DOI) and extranodal extension (ENE) into staging for oral squamous cell carcinoma (OSCC). Although validations have been performed on institutional datasets have shown a good performance, particularly in early OSCC, there have been no studies on diverse patient populations t...

To evaluate perceptions of a laryngeal cancer fact sheet amongst people with direct experience of the disease and its treatment. A mixed methods study (questionnaire and interview) evaluating the information resource was conducted across two institutions. In total 20 participants responded to the questionnaire. Overall participants reported the inf...

Background The prefabricated fibula flap is an advanced method of occlusal‐based reconstruction that combines placement of osseointegrated dental implants with prelamination, using a split skin graft on the fibula, weeks prior to the definitive reconstruction. This approach is resource intensive but has several advantages including eliminating the...

Cutaneous squamous cell carcinoma (cSCC) is a common skin cancer. Most patients who develop metastases (2–5%) present with advanced disease that requires a combination of radical surgery and adjuvant radiation therapy. There are few effective therapies for refractory disease. In this study, we describe novel patient-derived cell lines from cSCC met...

Purpose Metastases from cutaneous squamous cell carcinoma (cSCC) occur in 2-5% of cases. Surgery is the standard treatment, often combined with adjuvant radiotherapy. Concurrent carboplatin treatment with post-operative radiotherapy may be prescribed, although it has not shown benefit in recent clinical trials in high-risk cSCC patients. The novel...

Background: Nomenclature, classification, and management of parotid tumors are constantly evolving; this study was performed to identify temporal trends in histology and facial nerve sacrifice in parotidectomy during a 30-year period (1987-2018). Methods: Retrospective analysis of patients treated in a single tertiary-care institution during this t...

Background: The Sydney Facial Nerve Clinic (SFNC) is a multidisciplinary clinic established in 2015, consisting of surgeons (otolaryngologists, head and neck and plastics/reconstructive), physiotherapists and speech pathologists. Methods: We reviewed patients who attended the SFNC in the first 3 years and who had their symptoms recorded using th...

Background Soft tissue metastases (STMs) are reported to predict worse prognosis than extra-nodal extension (ENE) in metastatic head and neck cutaneous squamous cell carcinoma. This study aimed to update the authors’ previous analysis of STM in a larger series.Methods The study analyzed 535 cases of consecutive cSCC metastatic to the parotid and/or...

Background The volume-outcome relationship is a well-known phenomenon in surgical oncology. The aim of this study was to quantify the impact of surgeon volume on the treatment outcome of oral squamous cell carcinoma (OSCC) patients. Methods All new OSCC cases treated with curative intent between 2008 and 2013 were included. A heterogeneous set of...

Objectives: Prognostic significance of perineural invasion (PNI) in oral squamous cell carcinoma (OSCC) characterized as unifocal and multifocal was compared to depth of invasion (DOI) and extranodal extension (ENE). Materials and methods: Univariable and multivariable analyses of 861 consecutive patients with OSCC undergoing treatment between 1...

Background: This study assessed changes over time of survival of head and neck cutaneous squamous cell carcinoma (HNcSCC) with lymph node metastases. Methods: A multicenter analysis of 1301 patients with metastatic HNcSCC treated between 1980 and 2017. Differences in disease-specific survival (DSS) and overall survival (OS) by decade were assess...

Objective Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy, most frequently affecting the head and neck. Treatment often requires surgery and can have significant functional morbidity. Research into disease pathogenesis and second line medical management of cSCC is limited. We assess genetic mutations in high-risk, prim...

Background Head and neck cutaneous squamous cell carcinoma (HNcSCC) is one of the most common malignancies in Australia and consequently it is important to know whether patient outcomes have improved with time. Methods All patients with metastatic HNcSCC treated with curative intent were identified from the Sydney Head and Neck Cancer Institute da...

Purpose/Aim: Early cancer diagnosis is a critical component of comprehensive cancer control, however more than 50% of head and neck cancers (HNCs) are diagnosed at advanced stage. HNC patients from regional/remote areas have poorer survival than metropolitan patients. The study aim was to examine pathways to treatment for patients with HNC in NSW,...

Objective: Is there a relationship between decision-making preferences and psychological distress? Methods: Patients who had received treatment for head and neck cancer (HNC) at four institutions within NSW, Australia were invited to complete a single questionnaire. Results: Five hundred and ninety-seven patients completed the questionnaire. The ma...

Genetic Landscape of Head and Neck Cutaneous Squamous Cell Carcinoma and clinical implications

Background: Providing appropriate educational resources to patients with head and neck cancer (HNC) is important but challenging. The aim of this study was to determine Australian clinicians' perceptions of currently used HNC information resources. Methods: A purpose-designed questionnaire was disseminated electronically to clinician members of...

Aim: Debate in the literature continues concerning the prognosis of young patients (YP) with mucosal squamous cell carcinoma (mSCC). Several population studies demonstrate an increasing incidence of non-Human Papilloma Virus (HPV) related mSCC. No Australian studies have examined this patient population to date. We conducted a case matched analysis...

Background: The incidence of non-Human Papilloma Virus (HPV) associated Head and Neck Squamous Cell Carcinoma (HNSCC) in young patients (<50 years) is increasing globally. The molecular pathways involved in the development of HNSCC remain unexamined in this cohort. There are anecdotal reports of mismatch repair (MMR) protein loss in HNSCC. Also MMR...

Background: The prognostic impact of the size and number of nodal metastases in head and neck cutaneous squamous cell carcinoma (SCC) is well established. The purpose of this study was to validate the prognostic significance of the lymph node ratio in metastatic head and neck cutaneous SCC. Methods: A retrospective review of 326 patients with he...

Background: The American Joint Committee on Cancer (AJCC) uses the same nodal staging system for cutaneous and mucosal squamous cell carcinoma of the head and neck in its 8th edition (AJCC 8) despite differences in the etiology, risk factors, and clinical behavior of the two diseases. This study aims to evaluate the performance of the AJCC 8 nodal...

Purpose To determine the factors affecting outcome in surgically salvaged, locoregionally recurrent squamous cell carcinoma of the tongue (SCCT) Methods In a retrospective cohort of patients who underwent successful salvage of locoregionally recurrent SCCT we performed this observational analytical study to determine survival and their determinant...

Metastases to the parotid gland are the commonest cause of parotid malignancies in many regions of the world including Australia. The most common etiology of these metastases is head and neck cutaneous squamous cell carcinoma (HNcSCC) followed by melanoma of the head and neck. This article focuses on the management of the aforementioned pathologies...

Objectives The primary aim of this study is to compare the effect of using tumor thickness versus depth of invasion (DOI) to determine the 8th edition AJCC T-category on survival in a large cohort of OSCC. Materials and methods A retrospective cohort study of patients whose clinicopathologic information had been collected prospectively into a dedi...

Background: The 8th edition American Joint Committee on Cancer (AJCC8) provides the same nodal staging system for mucosal and cutaneous squamous cell carcinoma of the head and neck (HNcSCC) and includes extranodal extension (ENE) as an adverse prognostic criterion. This study evaluates the prognostic efficacy of the AJCC8 pathologic nodal staging...

Cutaneous squamous cell carcinoma is the second most prevalent malignancy, most frequently occurring in the head and neck (head and neck cutaneous squamous cell carcinoma). Treatment of locally advanced or metastatic disease is associated with functional morbidity and disfigurement. Underlying genetic mechanisms are poorly understood. Targeted sequ...

Salivary gland cancers are a complex group of tumours with variations in location, type and grade, all of which influence their biological behaviour. The understanding of salivary gland pathology has evolved at the molecular level in the last decade leading to identification of distinct entities, development of improved methods of diagnosis as well...

Background and objectives: The aim of this study is to analyze the clinical outcomes of patients who underwent bone resection for cutaneous malignancy of the face and scalp. Methods: We retrospectively collected patient data from 62 patients who underwent bone resection for craniofacial cutaneous malignancy of the face and scalp over the last 10...

Circumferential defects following salvage pharyngolaryngectomy present significant challenges in reconstructive surgery. The gastro-omental free flap has been shown to reduce the incidence of major fistula and catastrophic complications. The current technique for harvest of the flap requires laparotomy, which is potentially associated with signific...

Head and neck cutaneous squamous cell carcinoma (HNcSCC) can present with cervical metastases without an obvious primary. Immunohistochemistry for p16 is established as a surrogate marker of human papillomavirus (HPV) in oropharyngeal cancer. p16 expression in HNcSCC needs to be elucidated to determine its utility in predicting the primary site. Th...

Programmed cell death (PD-1) and its ligand (PD-L1) inhibitors have shown clinical response in many tumours. PD-L1 data are limited in head and neck cutaneous squamous cell carcinoma (HNcSCC) and no clinical trials of PD-1/PD-L1 inhibitors are published. We performed PD-L1 immunohistochemistry on 74 cases of high risk HNcSCC with 38 matched metasta...

Background: Salivary duct carcinomas (SDCa) are rare highly aggressive malignancies. Most patients die from distant metastatic disease within three years of diagnosis. There are limited therapeutic options for disseminated disease. Results: 11 cases showed androgen receptor expression and 6 cases showed HER2 amplification. 6 Somatic mutations wi...

Background: The immediate reconstruction of the face in the setting of radical parotidectomy for malignancy represents a particular challenge. We present a novel technique using 2 sections of the vastus lateralis muscle as a chimeric flap in combination with the anterolateral thigh (ALT) fasciocutaneous flap to achieve midface reanimation and eye...

Cutaneous squamous cell carcinoma (SCC) is second only in incidence to basal cell carcinoma (BCC), effecting up to 500?000 people in the United States annually. Metastasis to regional lymph nodes occurs in approximately 5% of cases and imparts significant morbidity. Standard treatment in this group involves a combination of surgery and adjuvant rad...

Background: The purpose of this study was to determine the effect of postoperative radiotherapy (PORT) on recurrence and survival in patients with oral squamous cell carcinoma (OSCC) of intermediate recurrence risk. Methods: Intermediate risk patients, defined as pT1, pT2, pN0, or pN1 with at least one adverse pathological feature (eg, lymphovas...

Introduction: Axonal excitability measures give insight into the biophysical properties of peripheral nerve axons. In this study we applied these techniques to the study of facial palsy. Methods: Thirty patients with established facial palsy due to unresolved Bell's palsy or herpes zoster (>6 months duration), tumor invasion of the facial nerve,...

Background: Facial paralysis remains a debilitating condition despite advances in medical, surgical and adjunctive interventions. Established grading systems used to assess facial paralysis and interventional outcomes have well described limitations. The Electronic Facial Paralysis Assessment (the eFACE), a clinician-graded zone-based facial funct...

Background: Head and neck cancer (HNC) encompasses a diverse group of tumors, and thus providing appropriate and tailored information to patients before, during, and after treatment is a challenge. The objective of the current study was to characterize the experience and unmet needs of patients with HNC with regard to information and support provi...

Background: Innervated free muscle transfer using the gracilis muscle or temporalis myoplasty has been successfully utilized for facial reanimation in chronic facial palsy. These techniques are less suited to immediate facial reconstruction in the setting of radical parotidectomy, in which the complexity of the defect, patient age, postoperative r...

Background: Metastatic cutaneous squamous cell carcinoma of the head and neck (cHNSCC) is more common in older patients. It is postulated that the age-related decline in immunity plays a role in cancer predisposition and prognosis. We aimed to investigate the effect of age on outcomes in cHNSCC and compare these with the outcomes of patients with...

Background: Significant oral function is often lost after surgical therapy for head and neck cancer. The use of osseointegrated implants for reconstruction in patients with head and neck surgery has shown to significantly improve the quality of life for these patients. Variable success rates range from 99% to 70%. Methods: A retrospective audit...

Purpose: Most Australians will be diagnosed with skin cancer during their lifetime. cSCC is the second most prevalent skin cancer, and most common lethal malignancy worldwide, with the head and neck a common site resulting in significant morbidity. This study sought to identify genomic alterations in a small cohort of patients with non-metastatic,...

The most devastating outcome of facial nerve paralysis is the inability to completely close the eye as it can lead to corneal ulceration and loss of vision. Gravity-assisted eye closure with upper lid loading is commonly used; however it is limited in replicating physiological eye closure to adequately lubricate the cornea. Superior results can be...

Phase 2 clinical trials utilising novel anti-PD1/PD-L1 antibodies are being conducted in oral cavity squamous cell carcinoma (OSCC) patients. However, data regarding PD-L1 expression in OSCC is limited. The aim of this study was to characterise the PD-L1 immunohistochemical expression in OSCC and its association with clinicopathological factors. Cl...

Background: Serum thyroglobulin is used as a surrogate marker for well-differentiated thyroid carcinoma recurrence. This study investigates whether thyroglobulin measured at the time of ablative radioactive iodine therapy predicts disease-free survival. Methods: A retrospective review was conducted of patients with well-differentiated thyroid ca...

Background: Circulating tumour cells (CTCs) are increasingly being used in the surveillance of cancer, allowing for potential early detection and real-time monitoring of disease progression. The presence of CTCs in patients with metastatic cutaneous head and neck squamous cell carcinoma (cHNSCC) has not been evaluated. Results: CTCs were detecte...

Background: Removal of part or all of the parotid gland may leave a visible contour defect and may also be associated with complications such as Frey's syndrome. These aesthetic and functional issues can be addressed using dermofat graft reconstruction. The aim of this study is to assess patient satisfaction and complications associated with using...

There is limited information regarding the incidence of p16 expression, its association with human papillomavirus (HPV) and prognosis in oral cavity squamous cell carcinoma (OSCC). The role of p16 in OSCC is evaluated in 215 cases using tissue microarrays (TMAs). p16 immunohistochemistry and HPV in situ hybridisation were performed on TMAs followin...

Background: There are many patient-based and clinician-based scales measuring the severity of facial nerve paralysis and the impact on quality of life, however, the social perception of facial palsy has received little attention. The purpose of this pilot study was to measure the consequences of facial paralysis on selected domains of social perce...

Objective: Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy, with a proportion harboring MAML2 rearrangement. This study evaluates the diagnostic and prognostic utility of MAML2 rearrangement in MEC. Study design: Salivary gland malignancies at a single institution (1989-2014) were reviewed to identify MECs. Histopatho...

Background: This study investigated the impact of adverse pathological features (APFs) amongst patients with T1N0 oral squamous cell carcinoma (OSCC) on both tumour control and survival. We aimed to investigate clinicopathological factors that would predict poor outcomes and determine a clinically relevant threshold for the recommendation of addit...

Background: Interaction of PD-L1 with the PD-1 receptor on T-cells negatively regulates T-cell function thereby promoting tumour-mediated immune evasion. Clinical trials of monoclonal anti-PD-1 antibodies have reported high response rates and improved survival in patients with a variety of malignancies. The efficacy of these treatments in OSCC is u...

Background The rates of oropharyngeal cancers such as tonsil cancers are increasing. The tumour suppressor protein Programmed Cell Death Protein 4 (PDCD4) has been implicated in the development of various human cancers and small RNAs such as microRNAs (miRNAs) can regulate its expression. However the exact regulation of PDCD4 by multiple miRNAs in...

Objectives: To assess whether small oral squamous cell carcinomas (OSCC) require the same margin clearance as large tumors. We evaluated the association between the ratio of the closest margin to tumor size (MSR) and tumor thickness (MTR) with local control and survival. Methods and methods: The clinicopathologic and follow up data were obtained...