The negative predictive value of FDG PET/CT staging in early oropharyngeal squamous cell carcinoma and implications to transoral robotic surgery patient selection.

OBJECTIVES: Our objective was to determine the negative predictive value (NPV) of preoperative FDG PET/CTfor detecting locoregional nodal disease. The aim was to help inform the decision-making process when identifying patients with early-stage OPSCC that would be suitable for transoral robotic surgery (TORS) as a single-modality treatment. MATERIALS AND METHODS: A retrospective cohort study was conducted of adults with primary stage cT1-2 OPSCC with up to one metastatic neck lymph node (cN0-1) planned for TORS. Patients with a preoperative PET/CT and who had undergone staging neck dissection (ND) were included. Clinical and pathological nodal staging was established based on PET/CT and ND, respectively. The primary outcome was the frequency of occult (not seen on PET/CT) nodal disease on ND. RESULTS: Eighty-eight patients were included (N = 88). The rate of occult nodal disease was 28.4 % (n = 25). The NPV of PET/CT in the clinically negative neck was 79 % and 66 % in cases with a single clinical node. Following staging ND, thetreatment plan changed in 27 % of cases overall, 7 % in cN0 and 36.7 % in cN1. Among these, 18 % met criteria for radiotherapy and 9 % for CRT. This represented a decrease in the number of ideal candidates for TORS as single-modality treatment from 88 to 64 (73 %). CONCLUSIONS: PET/CT is a useful tool in the workup of patients for primary TORS. However, about one third of patients with early-stage OPSCC might benefit from adjuvant therapy not predicted by preoperative PET/CT. A staging ND helps confirm candidates for single-modality treatment with TORS.

Use of telemedicine consultations in head and neck cancer: patient perceptions, acceptability and accessibility.

BACKGROUNDS: Telemedicine has been effective in the management of various medical conditions, however, there is limited knowledge of its use in head and neck oncosurveillance. This is of importance currently while trying to mitigate the risk of transmission during the COVID-19 pandemic. This study aims to evaluate acceptability, satisfaction and perceptions of telemedicine technology among outpatients for head and neck oncologic surveillance. METHODS: A cross-sectional study was conducted for head and neck surgical oncology patients who attended telemedicine consultations between March and October 2020 at the Peter MacCallum Cancer Centre. Data on demographic, socioeconomic and acceptability variables was collected, utilizing Likert scale questions. The primary outcome measures were patient satisfaction and perceptions, while the secondary outcome was access to technology. RESULTS: One hundred and fifteen patients were invited to participate, and 100 were included in the final analysis; 95% of patient's had a positive experience with telemedicine appointments and were willing to have future telemedicine appointments. Regional and rural patients were more accepting of telemedicine consultations, citing savings in travel time and the minimal disruption to normal day-to-day activities. All participants had access to telecommunication devices, with 63% having three or more devices. Issues identified include a lack of physical examination by clinician for 65% of participants and the inability to self-examine for 88% of participants. CONCLUSION: The study demonstrates patients' acceptance of telemedicine appointments as a component of outpatient surveillance for head and neck surgical oncology. This has benefits during the COVID-19 pandemic in addition to increasing accessibility for rural patients.

Immunotherapy to Avoid Orbital Exenteration in Patients With Cutaneous Squamous Cell Carcinoma.

BACKGROUND: Cutaneous squamous cell carcinoma (CSCC) of the head and neck can require complex and disfiguring surgery in order to achieve cure, which can be morbid and negatively impact patient quality of life. The management of advanced CSCC has been revolutionized by immunotherapy with current clinical trials also exploring its role in the neoadjuvant and adjuvant settings. Patients may decline morbid curative surgery, such as orbital exenteration, and the outcomes of immunotherapy use in this unique group of patients require further investigation. METHODS: We reviewed the records of 119 patients treated at a major Australian quaternary oncology centre with immunotherapy (either cemiplimab or pembrolizumab) for advanced CSCC. RESULTS: We identified 7 patients recommended curative surgery involving orbital exenteration after multidisciplinary discussion, who declined surgery due to concerns about morbidity and/or disfigurement. All 7 patients demonstrated a response to treatment, and six avoided orbital exenteration. Two patients experienced pseudoprogression. CONCLUSIONS: The management of CSCC can be complex and requires the input of a multidisciplinary team. Immunotherapy to avoid or reduce the extent of morbid definitive surgery is an emerging treatment option.

Management of Parotid Metastatic Cutaneous Squamous Cell Carcinoma: Regional Recurrence Rates and Survival.

Objectives Extent of parotidectomy and neck dissection for metastatic cutaneous squamous cell carcinoma (cSCC) to the parotid is debated. We describe our experience, analyzing outcomes (overall survival and regional recurrence) associated with surgical extent and adjuvant treatment. Study Design A retrospective cohort study of parotidectomy with or without neck dissection for metastatic cSCC. Setting A tertiary referral cancer center in Australia. Subjects and Methods The study group consisted of patients with metastatic cSCC involving the parotid gland who underwent a curative-intent parotidectomy (superficial or total), with or without neck dissection, between 2003 and 2014. Demographic and clinical data, treatment modalities, and outcome parameters were collected from the electronic institutional database. Results Of 78 patients, 65 underwent superficial parotidectomy. Median follow-up was 6.5 years. Sixty-four patients (82%) patients received adjuvant radiotherapy. Cervical lymph nodes were involved in 6 (24%) elective neck dissections. Involved preauricular, facial, external jugular, and occipital nodes occurred in 36.9%. Adjuvant radiotherapy was associated with improved 5-year survival-50% (95% CI, 36%-69%) versus 20% (95% CI, 6%-70%)-and improved 2-year regional control: 89% (95% CI, 67%-100%) versus 40% (95% CI, 14%-100%). The ipsilateral parotid bed recurrence rate was 3.7% for those who received adjuvant radiotherapy and 27% for those who did not receive radiotherapy. Conclusion This study supports surgery plus adjuvant radiotherapy as a standard of care for metastatic cSCC. The low incidence of parotid bed recurrence with this approach suggests that routine elective deep lobe resection may not be required.

Unilateral radiotherapy treatment for p16/human papillomavirus-positive squamous cell carcinoma of unknown primary in the head and neck.

OBJECTIVES/HYPOTHESIS: The outcomes of unilateral radiotherapy treatment for patients with p16/HPV-positive squamous cell carcinomas of unknown primary (SCCUP) affecting cervical lymph nodes are under-reported. Compared to radiating large volumes of the pharyngeal axis (the more common approach), this is potentially a much less toxic treatment for a good prognosis group. STUDY DESIGN: Retrospective cohort study. METHODS: We identified patients with SCCUP who were treated radically at our center and did not have parotid or isolated level IV or V nodal involvement. Failure-free and overall survivals were calculated using Kaplan-Meier methods. RESULTS: From 2004 to 2012, there were 49 radically treated patients with SCCUP. Fourteen patients had bilateral neck treatment (they had bilateral nodal disease or suspected lesions in the base of tongue, though not proven with biopsy), two had surgery alone, whereas 33 had unilateral radiotherapy (after neck dissection, excisional biopsy, or definitively with concurrent chemotherapy). Of the 33 patients, 21 tested positive to p16/HPV and had median follow-up of 57 months. In this group, no isolated contralateral neck failures or putative primaries emerged. There was 1/21 (4.3%) ipsilateral neck failure, 1/21 (4.3%) concurrent contralateral neck and distant failure, and 1/21 (4.3%) patient with distant failure. The 5-year freedom from failure was 78% (95% confidence interval [CI]: 56%-100%) and overall survival was 90% (95% CI: 79%-100%). CONCLUSIONS: With no emergence of putative primaries and no isolated contralateral neck failures, this single-institution experience in p16/HPV-positive SCCUP patients suggests that unilateral radiotherapy may be an underutilized management strategy. LEVELS OF EVIDENCE: 4 Laryngoscope, 128:2076-2083, 2018.

Obviating the need for sternotomy: Safety and effectiveness of microdebrider use for retrosternal goiter.

BACKGROUND: Most retrosternal goiter surgical removal can be performed via a transcervical approach. However, it is often a challenging procedure, which might include sternotomy. METHODS: We describe a surgical technique using a microdebrider for intracapsular volume reduction that precedes an extracapsular thyroidectomy, thereby avoiding the need for sternotomy, with decreased morbidity and risk. The procedure is described in detail with 2 representative cases and a summary of our experience in 26 cases. RESULTS: Twenty-six patients with retrosternal goiters are included in our cohort. None of the patients needed a sternotomy, and no major or permanent complications occurred. The average length of hospital stay was 4.30 days after total thyroidectomy and 2.57 days after hemithyroidectomy. CONCLUSION: The use of a microdebrider for intracapsular volume reduction thyroidectomy is extremely helpful for transcervical removal of retrosternal goiters in selected cases, and avoids the need for sternotomy, which is especially beneficial in elderly patients, and those with comorbidities for whom sternotomy should be avoided.

Transoral robotic surgery: implementation as a tool in head and neck surgery - a single-centre Australian experience.

BACKGROUND: Transoral robotic surgery (TORS) is now a well-validated technique for resection of head and neck cancers. Benefits include reduced patient morbidity, swallowing preservation and rationalization of adjuvant therapies. METHODS: This was a single-centre, retrospective review of 35 patients who underwent TORS of oro-, retro- and parapharyngeal tumours between March 2014 and August 2015. Outcome measures included resection margins, swallowing function and impact on post-operative radiotherapy. RESULTS: Median age was 63.7 years and the number of male patients was 22 (62.9%). Tongue base was the most common site (51.4%), followed by tonsil (25.7%). Nine patients (25.7%) had previous radiotherapy. A total of 24 patients had squamous cell carcinoma and the clear margin rate for primary TORS was 93.3%. Median hospital stay was 5.5 days, longer for previously irradiated patients (9 days). Median nasogastric tube dependence was 3.5 days. Four patients (11.4%) received a gastrostomy and two patients remained dependent on the tube at the time of last review. There were two major complications (5.7%): bleeding requiring return to theatre (1) and pulmonary embolism (1). Post-operative radiotherapy was either avoided or reduced in 22 patients (81.5%). CONCLUSION: TORS is a safe and effective tool, providing surgical access to oropharyngeal and other difficult to access areas. Patient selection and a multidisciplinary approach are essential to ensure adequate margins can be achieved and therefore to reduce adjuvant therapies.

Retropharyngeal lipoma causing obstructive sleep apnoea.

We present the case of a middle-aged man whose obstructive sleep apnoea (OSA) was caused by a retropharyngeal lipoma, with complete resolution after transoral excision. Lipomas causing OSA are rare, and this represents the seventh reported case in the literature.

Prognostic markers in metastatic cutaneous squamous cell carcinoma of the head and neck.

BACKGROUND: The minority of head and neck cutaneous squamous cell carcinomas (SCC) metastasize to regional lymph nodes. The purpose of this study was to describe the clinical outcomes and prognostic factors for patients with node-positive head and neck cutaneous SCC who underwent lymphadenectomy. METHODS: We conducted a retrospective single center study using the Kaplan-Meier method for the investigation of the overall survival (OS) and locoregional control rates. The Cox proportional hazards model was evaluated to identify prognostic factors. RESULTS: The median number of positive lymph nodes from 149 lymphadenectomies was 2 in the neck and 1 in the parotid gland. The 5-year OS and locoregional control rates were 50% and 77%, respectively. OS was worse among older patients (hazard ratio [HR], 1.04; p = .015), immunosuppressed patients (HR, 2.06; p = .034), and patients with a high total lymph node ratio (calculated from the number of positive lymph nodes divided by the total number of nodes; multivariate analysis [MVA]; HR, 1.13; p = .019). CONCLUSION: Low total lymph node ratio is associated with improved outcomes in node-positive head and neck cutaneous SCC. © 2017 Wiley Periodicals, Inc. Head Neck 39: 772-778, 2017.

Outcomes of cutaneous squamous cell carcinoma of the head and neck with parotid metastases.

INTRODUCTION: Cutaneous squamous cell carcinoma of the head and neck (cHNSCC) metastatic to the parotid has a moderate risk of recurrence despite multimodality treatment. Immunosuppression is associated with lower rates of long-term cure. Our aim was to review outcomes of current management in a tertiary centre with a view to targeting future strategies. METHODS: A retrospective review of clinico-pathological data and outcomes for patients with metastatic cHNSCC involving the parotid gland, undergoing radical surgery and adjuvant radiotherapy during 2000-2014 was conducted. The Kaplan-Meier method was used to determine time-to-event outcomes. RESULTS: One hundred and thirty-two patients met the inclusion criteria. Median follow-up was 5.0 years. Five-year overall (OS), cancer-specific (CSS) and progression free survival (PFS) were 44% (95% Confidence Interval (CI) 34-53%), 64% (95% CI 52-74%) and 37% (95% CI 28-47%) respectively. Locoregional control (LRC) was 68% (95% CI 55-77%) at 5 years. Immunosuppressed patients fared worse (compared with immune-competent) with five-year OS, CSS, and PFS of 14% versus 53% (HR = 3.19; 95% CI 1.91-5.34), 40% versus 71% (Hazard Ratio (HR) = 2.92; 95% CI 1.38-6.19) and 10% versus 46% (HR = 2.51; 95% CI 1.52-4.14) respectively. On multivariate analysis, immune status strongly predicted OS (P < 0.001), CSS (P = 0.003), DMFS (P < 0.001) and PFS (P < 0.001), but not LRC. Largest lymph node size was the only significant factor predictive for LRC on multivariate analysis (P = 0.02). CONCLUSIONS: Despite multimodality treatment metastatic cHNSCC involving the parotid shows moderate rates of recurrence. Immunosuppressed patients with this disease have a particularly poor prognosis, demonstrating lower rates of CSS with similar rates of LRC compared to their immunocompetent counterparts.

p16-positive lymph node metastases from cutaneous head and neck squamous cell carcinoma: No association with high-risk human papillomavirus or prognosis and implications for the workup of the unknown primary.

BACKGROUND: The incidence of p16 overexpression and the role of human papillomavirus (HPV) in cutaneous head and neck squamous cell carcinoma (cHNSCC) are unclear. METHODS: One hundred forty-three patients with cHNSCC lymph node metastases involving the parotid gland were evaluated for p16 expression by immunohistochemistry. The detection of 18 high-risk HPV subtypes was performed with HPV RNA in situ hybridization for a subset of 59 patients. The results were correlated with clinicopathological features and outcomes. RESULTS: The median follow-up time was 5.3 years. No differences were observed in clinicopathological factors with respect to the p16 status. p16 was positive, weak, and negative in 45 (31%), 21 (15%), and 77 cases (54%), respectively. No high-risk HPV subtypes were identified, regardless of the p16 status. The p16 status was not prognostic for overall (hazard ratio, 1.08; 95% confidence interval [CI], 0.85-1.36; P = .528), cancer-specific (hazard ratio, 1.12; 95% CI, 0.77-1.64; P = .542), or progression-free survival (hazard ratio, 1.03; 95% CI, 0.83-1.29; P = .783). Distant metastasis-free survival, freedom from locoregional failure, and freedom from local failure were also not significantly associated with the p16 status. CONCLUSIONS: p16 positivity is common but not prognostic in cHNSCC lymph node metastases. High-risk HPV subtypes are not associated with p16 positivity and do not appear to play a role in this disease. HPV testing, in addition to the p16 status in the unknown primary setting, may provide additional information for determining a putative primary site.

Benign neck metastasis of a testicular germ cell tumor.

Germ cell tumors (GCTs) are relatively rare neoplasms considered to be curable malignancies since the introduction of cisplatin. The presence of neck metastasis has been reported, with fewer reports of metastatic mature teratoma. In this study, 3 cases of "benign neck" metastasis in patients with GCT between 1998 and 2010 were reviewed retrospectively. In all 3 cases the presenting clinical sign was a left lower neck mass, leading to the diagnosis of the primary site in the testis. All had surgical salvage following chemotherapy, with benign lesions or mature teratoma in histopathology of the neck mass. Chemotherapy was followed by salvage lower-half neck dissection showing benign features in the neck specimen, even though malignancy was proven histologically in other areas. Only 1 patient had a postoperative chyle leak, which resolved spontaneously after several days. Neck dissection is recommended in those patients because malignancy cannot be excluded.

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.

T4 squamous cell carcinoma of the oral tongue without mandibular involvement: surgery or chemoradiotherapy?

OBJECTIVE: To investigate disease control and functional outcomes in patients with T4 squamous cell carcinoma of the oral tongue who had undergone surgery or definitive chemoradiotherapy. STUDY DESIGN: Records of all consecutive patients with T4 squamous cell carcinoma of the oral tongue treated radically between 1999 and 2010 at the Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia, were retrospectively reviewed. RESULTS: Of 31 patients, 19 underwent surgery and 12 underwent definitive chemoradiotherapy. There were no significant differences between cohorts in terms of age, nodal involvement, or performance status. All patients had T4 disease on the basis of extrinsic muscle invasion; none had bone invasion. Disease outcomes at 5 years after surgery or chemoradiotherapy were not significantly different, including local control (61% vs 70%), progression-free rate (56% vs 55%), and overall survival (27% vs 40%). A higher proportion of patients in the chemoradiotherapy group had only mild impairment of speech and swallowing. CONCLUSIONS: Definitive chemoradiotherapy may be a reasonable alternative to surgery for patients with T4 squamous cell carcinoma of the oral tongue without bony invasion.

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.

Larynx preservation for patients with locally advanced laryngeal cancer.

A 53-year-old man presented with a 6-month history of mild hoarseness, with no associated pain, dysphagia, or stridor. At nasoendoscopy, a lesion was detected involving the whole length of the left vocal cord, with abnormal mucosa also seen in the right ventricle (Fig 1). The left vocal cord movement was impaired. There were no palpable neck nodes. Biopsy under anesthesia revealed moderately differentiated squamous cell carcinoma. He was a current smoker of 30 cigarettes per day (45 pack-year smoking history), and he consumed four standard drinks of alcohol per day. His Eastern Cooperative Oncology Group performance status was 1, and he had no significant comorbidities. Radiologic review of his outside computed tomography scan noted that it was of poor quality, and a magnetic resonance imaging scan was recommended, which showed low-volume T4a disease based on focal thyroid cartilage penetration (Fig 2). A positron emission tomography (PET) scan revealed no evidence of nodal or distant metastasis.