Development and validation of a novel TNM staging N-classification of oral cavity squamous cell carcinoma.

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 centers were included and extent of ENE was recorded. Thresholds for optimal overall survival (OS) discrimination of lymph node (LN) features were established. After dividing into training and validation sets, two new N-classifications were created using 1) recursive partitioning analysis (RPA), and 2) adjusted hazard ratios (aHRs) and were ranked against TNM-8-N and two published proposals. RESULTS: A total of 1460 patients were included (pN0: 696; pN+: 764). Of the pN+ cases, 135 (18%) had bilateral/contralateral LNs; 126 (17%) and 244 (32%) had minor and major ENE, and two (0.3%) had LN(s) >6 cm without ENE (N3a). LN number (1 and >1 vs. 0: aHRs, 1.92 [95% confidence interval (CI), 1.44-2.55] and 3.21 [95% CI, 2.44-4.22]), size (>3 vs. ≤3 cm: aHR, 1.88 [95% CI, 1.44-2.45]), and ENE extent (major vs. minor: aHR, 1.40 [95% CI, 1.05-1.87]) were associated with OS, whereas presence of contralateral LNs was not (aHR, 1.05 [95% CI, 0.81-1.36]). The aHR proposal provided optimal performance with these changes to TNM-8-N: 1) stratification of ENE extent, 2) elimination of N2c and 6-cm threshold, and 3) stratification of N2b by 3 cm threshold. CONCLUSION: A new N-classification improved staging performance compared to TNM-8-N, by stratifying by ENE extent, eliminating the old N2c category and the 6 cm threshold, and by stratifying multiple nodes by size.

Comparing Genomic Landscapes of Oral and Cutaneous Squamous Cell Carcinoma of the Head and Neck: Quest for Novel Diagnostic Markers.

Squamous cell carcinoma is the most common head and neck malignancy arising from the oral mucosa and the skin. The histologic and immunohistochemical features of oral squamous cell carcinoma (OSCC) and head and neck cutaneous squamous cell carcinoma (HNcSCC) are similar, making it difficult to identify the primary site in cases of metastases. With the advent of immunotherapy, reliable distinction of OSCC and HNcSCC at metastatic sites has important treatment and prognostic implications. Here, we investigate and compare the genomic landscape of OSCC and HNcSCC to identify diagnostically useful biomarkers. Whole-genome sequencing data from 57 OSCC and 41 HNcSCC patients were obtained for tumor and matched normal samples. Tumor mutation burden (TMB), Catalogue of Somatic Mutations in Cancer (COSMIC) mutational signatures, frequent chromosomal alterations, somatic single nucleotide, and copy number variations were analyzed. The median TMB of 3.75 in primary OSCC was significantly lower (P < .001) than that of 147.51 mutations/Mb in primary HNcSCC. The COSMIC mutation signatures were significantly different (P < .001) between OSCC and HNcSCC. OSCC showed COSMIC single-base substitution (SBS) mutation signature 1 and AID/APOBEC activity-associated signature 2 and/or 13. All except 1 HNcSCC from hair-bearing scalp showed UV damage-associated COSMIC SBS mutation signature 7. Both OSCC and HNcSCC demonstrated a predominance of tumor suppressor gene mutations, predominantly TP53. The most frequently mutated oncogenes were PIK3CA and MUC4 in OSCC and HNcSCC, respectively. The metastases of OSCC and HNcSCC demonstrated TMB and COSMIC SBS mutation signatures similar to their primary counterparts. The combination of high TMB and UV signature in a metastatic keratinizing squamous cell carcinoma suggests HNcSCC as the primary site and may also facilitate decisions regarding immunotherapy. HNcSCC and OSCC show distinct genomic profiles despite histologic and immunohistochemical similarities. Their genomic characteristics may underlie differences in behavior and guide treatment decisions in recurrent and metastatic settings.

Whole genome duplication in oral squamous cell carcinoma in patients younger than 50 years: implications for prognosis and adverse clinicopathological factors.

INTRODUCTION: Oral squamous cell carcinoma (OSCC) in the young (<50 years), without known carcinogenic risk factors, is on the rise globally. Whole genome duplication (WGD) has been shown to occur at higher rates in cancers without an identifiable carcinogenic agent. We aimed to evaluate the prevalence of WGD in a cohort of OSCC patients under the age of 50 years. METHODS: Whole genome sequencing (WGS) was performed on 28 OSCC patients from the Sydney Head and Neck Cancer Institute (SHNCI) biobank. An additional nine cases were obtained from The Cancer Genome Atlas (TCGA). RESULTS: WGD was seen in 27 of 37 (73%) cases. Non-synonymous, somatic TP53 mutations occurred in 25 of 27 (93%) cases of WGD and were predicted to precede WGD in 21 (77%). WGD was significantly associated with larger tumor size (p = 0.01) and was frequent in patients with recurrences (87%, p = 0.36). Overall survival was significantly worse in those with WGD (p = 0.05). CONCLUSIONS: Our data, based on one of the largest WGS datasets of young patients with OSCC, demonstrates a high frequency of WGD and its association with adverse pathologic characteristics and clinical outcomes. TP53 mutations also preceded WGD, as has been described in other tumors without a clear mutagenic driver.

Oral Epithelial Dysplasia: A Review of Diagnostic Criteria for Anatomic Pathologists.

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 challenge, primarily due to its histologic mimics and a large number of terminologies used in the literature. The grading system for OED is also fraught with significant interobserver variability. This review summarizes the essential clinical and histopathologic features of OED and its mimics. Practical preanalytical, analytical, and postanalytical considerations for anatomic pathologists are discussed to improve the diagnostic accuracy and increase the reproducibility in the grading of OED.

Validation of the eighth edition AJCC staging system in early T1 to T2 oral squamous cell carcinoma.

BACKGROUND: To validate the newly proposed American Joint Committee on Cancer (AJCC) eighth edition staging in early T1 and T2 oral cavity cancers and its effect in predicting tumour control. METHODS: Retrospective analysis of treatment outcomes of 441 T1 to T2 oral squamous cell carcinoma (OSCC). Overall survival (OS), disease-specific survival (DSS), and tumour control were calculated and compared between the AJCC 7 and 8 staging systems. RESULTS: The 5-year OS was 78% and 61% for T1 and T2 tumours, respetively (P < 0.001) (AJCC 7) vs 87% and 67% (P < 0.001) (AJCC 8). The 5-year DSS was 78% and 61% for T1 and T2, respectively (P < 0.001) (AJCC 7) vs 89% and 71% (P < 0.001) (AJCC 8). For stages I and II tumours the 5-year OS was 81% and 76%, respectively (P < 0.302) (AJCC 7) vs 87% and 73% (P < 0.017) (AJCC 8). The 5-year DSS was 83% and 82% (P < 0.222) vs 89% and 77% (P < 0.016). With the AJCC eighth edition the 5-year local, regional, and distant control rates for T1 vs T2 tumours were 85% vs 74% (P = 0.003), 95% vs 77% (P = 0.001), and 95% vs 80% (P = 0.014), respectively. CONCLUSION: The AJCC 8th staging system provided for more accurate prediction of OS, DSS, and disease control in early oral cavity cancers.

Analysis of clinically relevant somatic mutations in high-risk head and neck cutaneous squamous cell carcinoma.

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 sequencing of 48 clinically relevant genes was performed on DNA extracted from formalin-fixed and paraffin-embedded high-risk primary head and neck cutaneous squamous cell carcinomas that remained non-metastatic at minimum follow-up of 24 months. Associations of somatic mutations with clinicopathologic characteristics were evaluated and compared with those described in the literature for metastatic disease. Alterations in 44 cancer-associated genes were identified. TP53 was mutated in 100% of cases; APC, ATM, ERBB4, GNAQ, KIT, RB1 and ABL1 were altered in 60% of cases. FGFR2 mutations (40%) were exclusively seen in patients with perineural invasion. MLH1 mutations were exclusively seen in the two younger patients (<45 years). Lower incidences of NOTCH1 mutations were observed compared with that described in metastatic head and neck cutaneous squamous cell carcinoma in the literature. Somatic mutations susceptible to EGFR inhibitors, and other small molecular targeted therapeutics were seen in 60% of cases. This study provides insights into somatic mutations in non-metastatic, high-risk head and neck cutaneous squamous cell carcinoma and identifies potential therapeutic targets. Alterations in FGFR2 and NOTCH1 may have roles in local and distant disease progression.

Analysis and Comparison of the 8th Edition American Joint Committee on Cancer (AJCC) Nodal Staging System in Cutaneous and Oral Squamous Cell Cancer of the Head and Neck.

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 staging system by direct comparison of cutaneous (cSCC) versus oral squamous cell carcinoma (oSCC) patients. METHODS: Patients with metastatic cSCC (N = 382) and oSCC (N = 325) were identified from a prospective database (years 1987-2016). Multivariable analysis was performed using Cox proportional hazards competing risk model. To assess staging system performance, an explained variation measure (proportion of variation explained, PVE) as well as a discrimination measure (Harrell's concordance index, C-index) were used. RESULTS: Inclusion of extranodal extension (ENE) in AJCC 8 increased the proportion of patients in N3b category (48.7% in cSCC, 40.3% in oSCC). AJCC 8 stratified poorly with regards to risk of death from cSCC and oSCC and showed limited monotonicity of the nodal categories. Estimates of model performance revealed modest predictive capacity for overall survival (OS) and disease-specific survival (DSS) in oSCC (Harrell's C of 0.66 in both) and weak predictive capacity in cSCC (Harrell's C of 0.58 and 0.61, respectively). CONCLUSIONS: The AJCC 8 nodal staging system performs poorly in terms of stratifying survival by N category, especially in cSCC. The data indicate that cSCC merits an independent nodal staging system from that for mucosal SCC.

Predictive value of the 8th edition American Joint Commission Cancer (AJCC) nodal staging system for patients with cutaneous squamous cell carcinoma of the head and neck.

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 system (pN) for HNcSCC. METHODS: Univariate analysis of 382 patients with metastatic HNcSCC staged according to both the 7th (AJCC7) and the 8th edition staging systems. RESULTS: The AJCC7 pN3 category was associated with reduced disease specific survival (DSS HR 5.49; 95% CI: 1.83-16.53; P = 0.002) and overall survival (OS HR 3.42; 95% CI: 1.54-7.58; P = 0.002) as compared with pN1. However, no difference was observed between pN1, pN2, and pN3 categories as defined by the AJCC8. Also, when comparing Stages III and IV as defined by AJCC8, there was no difference in DSS (HR 0.75; 95% CI: 0.34-1.67; P = 0.478) or OS (HR 0.88; 95% CI: 0.51-1.51; P = 0.648). CONCLUSION: The AJCC8 performed poorly as a prognostic indicator for patients with metastatic HNcSCC in this cohort. HNcSCC would benefit from a staging system that accounts for its unique biologic characteristics distinct from mucosal SCC.

Factors Affecting Survival in Surgically Salvaged Locoregional Recurrences of Squamous Cell Carcinoma of the Tongue.

PURPOSE: To determine the factors affecting outcomes in surgically salvaged, locoregionally recurrent squamous cell carcinoma of the tongue (SCCT). MATERIALS AND 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 its determinants. Details extracted from our database were patient characteristics (age, gender, tobacco use), treatment characteristics, and characteristics of recurrent disease (stage and adverse pathologic features [APFs] such as grade, perineural invasion, and lymphovascular invasion). Overall survival (OS) curves were plotted using the Kaplan-Meier method. A Cox proportional hazards model was used to determine the impact of patient, disease, and treatment characteristics on OS. RESULTS: Of 52 patients with locoregional recurrences of surgically treated SCCT, 25 (48.1%) underwent surgical salvage with curative intent. The median overall OS for this cohort was 26 months. Factors predictive of worse OS were previous adjuvant therapy (P = .016) and increasing APFs in recurrent tumor histology (P = .008). Lymphovascular invasion in recurrent tumor histology and patients with a disease-free interval of less than 6 months showed worse survival (P = .008 and P = .058, respectively). CONCLUSIONS: Among patients with locoregional recurrence, the number who are eligible for curative-intent surgical salvage is small. Those who received previous adjuvant therapy and those with increasing APFs in recurrent tumors had poor outcomes despite attempts at surgical salvage, particularly patients with early recurrence.

Reconstruction of maxillary defect with musculo-adipose rectus free flap.

BACKGROUND: The rectus myocutaneous free flap (RMFF) is used for medium to large maxillectomy defects. However, in patients with central obesity the inset could be difficult due to the bulk from excessive layer of adipose tissue. We describe a modification of the RMFF for patients with excessive central obesity with a flap consisting of adipose tissue with minimal rectus muscle; the musculo-adipose rectus free flap (MARF). METHODS: Five cases of MARF reconstruction were performed between 2003 and 2013, with patients' body mass indexes ranging from 29.0 to 41.2 kg/m2 . All patients had sinonasal tumor, of which three were adenoid cystic carcinoma, one squamous cell carcinoma, and one melanoma. Four patients had Codeiro IIIb defects and one had Codeiro II defect. Using the MARF technique, the maxillectomy defect was obliterated with vascularized adipose tissue overlying the rectus muscle and was trimmed to fit the maxillectomy defect. The adipose tissue was allowed to granulate and mucosalize. RESULTS: The volume of adipose tissue harvested was between 120 and 160 mL. All flaps survived with no requirement for re-exploration. Complete oro-nasal separation was achieved in all patients. The time to commencement of oral intake ranges from 5 to 15 days. One patient developed seroma and one developed wound breakdown on the donor site. The length of stay at the hospital ranges from 9 to 22 days. On follow-up ranging 7.5-32.8 months, two patients died from their malignancies. The other three patients were able to tolerate oral soft diet. CONCLUSION: The MARF may be considered as an alternative to myocutaneous rectus free flap particularly for the reconstruction of maxillary defects in patients with central obesity. © 2015 Wiley Periodicals, Inc. Microsurgery 37:137-141, 2017.

Perineural invasion in oral squamous cell carcinoma: quantitative subcategorisation of perineural invasion and prognostication.

BACKGROUND: Evidence regarding the prognostic value of perineural invasion (PNI) in oral squamous cell carcinoma (OSCC) and whether PNI alone warrants consideration of adjuvant therapy is controversial. We evaluated whether histopathological sub-categorization of PNI improves risk stratification. METHODS: PNI was evaluated for nerve size, number of foci, and distance from the tumor in 318 OSCC patients. Univariable and multivariable analyses were performed, with local failure (LF) and disease-specific survival (DSS) as the primary endpoints. RESULTS: PNI did not influence prognosis when classified as absent versus present. In contrast, multifocal PNI was associated with LF (P = 0.049) and decreased DSS (P = 0.043) on multivariable analyses. The size of the involved nerve separated those with multifocal PNI into intermediate (<1 mm) and high-risk (≥1 mm) groups. Unifocal PNI and distance from the tumor did not influence prognosis. Multifocal PNI was associated with worse prognosis irrespective of post-operative radiotherapy (PORT). CONCLUSIONS: Multifocal PNI is associated with poor outcomes even with PORT suggesting consideration of therapeutic escalation, particularly with involved nerves ≥1 mm. Unifocal PNI did not affect prognosis even in the absence of PORT, which may not be required if this is the sole risk factor. Prospective validation and testing of these hypotheses is essential before implementation.

A comparison of preoperative soft tissue contour versus bone accuracy as a predictor of quality of life outcomes in osseous free flap jaw reconstruction using occlusal-based virtual surgical planning.

OBJECTIVES: Occlusal-based virtual surgical planning (VSP) prioritises the placement of endosseous dental implants, over replicating native bone contour. This may compromise facial aesthetics. This study aimed to compare function and health-related quality of life (HRQOL) following maxillomandibular reconstruction according to the ability to replicate preoperative soft-tissue contour and virtual plan. MATERIALS AND METHODS: Patients who underwent occlusal based VSP osseous free flap reconstruction of the maxilla or mandible with high-resolution pre- and post-operative facial computerised tomography imaging and completed the FACE-Q questionnaire were retrospectively identified. Accuracy of reconstruction compared to preoperative soft tissue contour and virtual plan, was measured using 3DSlicer® and CloudCompare® in three dimensions. Random effects modelling determined the associations between bony and soft tissue accuracy and HRQOL/functional domains. RESULTS: Twenty-two patients met the inclusion criteria. For mandibular and maxillary reconstructions, better soft tissue accuracy was associated with improved appearance (p = 0.048) and appearance distress (p = 0.034). For mandibular reconstructions, better soft tissue accuracy was associated with improved smile (p = 0.039) and smile distress (p = 0.031). For maxillary reconstructions, better bony accuracy was associated with improved appearance (p = 0.023) and drooling distress (p = 0.001). Unexpectedly, better bony accuracy was associated with worse eating and drinking (p = 0.015), oral competence (p = 0.005) and eating distress (p = 0.013) in mandibular reconstructions. CONCLUSION: Whilst soft tissue accuracy was associated with better functional and HRQOL outcomes, bone accuracy was associated with worse oral function or distress in mandibular reconstruction. These results require validation but should be considered when performing occlusal-based VSP, which prioritises dental rehabilitation over replicating facial bony contour.

Acceptance and willingness of patients with chronic facial nerve palsy for an implantable device that assists with eye closure.

BACKGROUND: Patients with facial nerve palsy often experience lagophthalmos (incomplete eye closure), which can lead to exposure keratitis. The Bionic Lid Implant for Natural Eye Closure (BLINC) is a medical device designed to mimic the more natural blink kinetics than traditional lid loading techniques. AIMS: This study aimed to evaluate potential factors that might influence the design of the BLINC device and willingness of participant to undergo the implant placement surgery. METHODS: Patients attending a multidisciplinary facial nerve clinic were invited to complete a survey addressing patient acceptance of the BLINC device implantation. RESULTS: Seventy-two patients were mailed the survey, of which 50 returned completed surveys (69%). The most important factor identified by participants was the device function (81% ranked as very important) and the least important factor was cost (16% ranked as very important). Median acceptable device function time was 5 years (range 1-10 years). Ten participants (20%) indicated willingness to be the first to trial BLINC. Women were more likely to rate visual appearance as important (OR 3.32, CI 1.14-9.62, p = 0.028), and less likely to rate user friendliness as important (OR 0.16, CI 0.04-0.52, p = 0.0021). Older participants were more likely to rate the length of recovery period as important (OR 1.04, CI 1.01-1.08, p = 0.006). Participants with complete eye closure were less likely to be willing to trial the implant (OR 0.08, CI 0.00-0.53, p = 0.006, whilst patients with eye irritation were more willing to trial the implant (OR 7.20, CI 1.12-142, p = 0.036). CONCLUSION: Certain patient demographics impact patient aesthetic and functional preferences and the willingness to trial the BLINC device.

Surgical and health related quality of life outcomes following treatment with zygomatic implant perforated (ZIP) flaps.

BACKGROUND: The zygomatic implant perforated (ZIP) flap is a novel approach to the challenge of reconstructing the maxilla. We report on our experience using the ZIP flap technique for patients undergoing infrastructure maxillectomy at Chris O'Brien Lifehouse, Sydney, Australia. METHODS: Thirteen patients who underwent a ZIP flap reconstruction between August 2019 and August 2021 were identified. Demographic, surgical, and histopathological information was collected. Health Related Quality of Life (HRQOL) was assessed using the FACE-Q Head and Neck Cancer module, the M.D. Anderson Dysphagia Inventory, and the Speech Handicap Index. RESULTS: A total of 44 zygomatic implants were placed, of which 42 (95%) survived. The median time from surgery to dental rehabilitation was 35 days. HRQOL data was available for nine patients over 24 months, demonstrating improved speech and swallowing outcomes over the follow up period. CONCLUSIONS: The ZIP flap is a reproducible surgical technique that facilitates rapid dental rehabilitation post infrastructure maxillectomy.

When should patients with T1N0 oral squamous cell carcinoma be considered for elective neck dissection?

AIMS: To identify adverse pathological features (APF) predicting nodal failure in clinically node negative T1 oral squamous cell carcinoma (OSCC). METHODOLOGY: This study evaluated patients with T1N0 (≤5 mm depth of invasion (DOI) and ≤2 cm diameter) oral cancers from a prospectively maintained database between 1988 and 2020. All patients underwent surgical excision of the primary lesion without neck dissection. Patients underwent three monthly clinical surveillance and salvage neck dissection was performed if nodal relapse was diagnosed. RESULTS: Overall, 141 patients were included. Nodal relapse was reported in 16/141 (11.3%) patients. Factors impacting regional recurrence-free survival were DOI ≥3 mm (HR: 2.4, P < 0.001), maximum tumour diameter ≥12 mm (HR: 1.1, P = 0.009), perineural invasion (PNI) (HR 7.5, P = 0.002) and poor differentiation (HR 5.3, P = 0.01). Rates of nodal relapse increased from 2% amongst patients with no APFs to 100% for those with four APFs. Patients with two or more APFs had significantly poorer 5-year regional recurrence-free survival (94.8% vs. 56.3%, P < 0.001). CONCLUSION: Patients with T1N0 OSCC with two or more APFs (DOI ≥3 mm, diameter ≥12 mm, PNI or poor differentiations) should be considered for elective neck dissection.

A qualitative exploration of the pathway to diagnosis and treatment of cutaneous squamous cell carcinoma of the head and neck with perineural spread.

BACKGROUND: Perineural spread (PNS) is associated with a poor prognosis in cutaneous squamous cell carcinoma of the head and neck (cSCCHN). Hence, investigating facilitators and barriers of early diagnosis and treatment of PNS in cSCCHN may improve outcomes. METHODS: Patients were recruited from an institutional database. Semi-structured interviews were conducted according to the Model of Pathways to Treatment. Thematic analysis was based on the four main intervals in the framework using a data-driven analytical method. RESULTS: Seventeen participants were interviewed. Facilitators included patients' past experiences, symptom progression, trust in healthcare professionals (HCPs), and capacity to leverage relationships. Barriers included difficult diagnoses, limited access to cancer services, lack of care coordination, and lack of awareness of PNS among primary health care providers. CONCLUSION: These findings emphasise the complexity early diagnosis and treatment of PNS. Interventions like clinical practice guidelines, education for HCPs, and telehealth could facilitate timely detection and management.

Determinants of Prognosis in Head and Neck Cutaneous Squamous Cell Carcinoma With Nodal Metastases.

Importance: The eighth edition tumor, node, metastasis (TNM) staging for head and neck cutaneous squamous cell carcinoma (HNcSCC) is a poor predictor of survival in patients with lymph node metastases, possibly due to the inclusion of extranodal extension (ENE). Objective: To identify the key determinants of prognosis in patients with nodal metastatic HNcSCC and analyze the association of ENE with TNM stage and investigate for prognostic heterogeneity in ENE-positive disease. Design, Setting, and Participants: This retrospective, multicenter cohort study was conducted at 4 Australian tertiary referral centers using prospectively collected data in patients treated between 1980 and 2017 with a median (IQR) follow-up of 3.2 (3.9) years. The study population included 1309 consecutive patients with HNcSCC that was metastatic to parotid and/or cervical nodes. After excluding cases with perioperative mortality, missing data, or follow-up, the final study population included 1151 patients. Exposure: Curative intent surgery ± adjuvant radiotherapy. Main Outcomes and Measures: Differences in locoregional control (LRC), disease-specific survival (DSS), and overall survival were determined using Cox regression analysis. Results: Among 1151 patients, 976 (84.8%) were male and 175 (15.2%) female, with a median age of 73.3 years (range, 18-100 years). On multivariable analysis, immunosuppression (hazard ratio [HR], 2.48; 95% CI, 1.64-3.74), perineural invasion (HR, 1.69; 95% CI, 1.25-2.30), ENE (HR, 1.53; 95% CI, 0.95-2.44), size (>3-6 cm vs ≤3 cm [HR, 1.41; 95% CI, 1.03-1.93]; >6 cm vs ≤3 cm [HR, 5.01; 95% CI, 2.98-8.42]), and number of nodal metastases (3-4 vs 1-2 [HR, 1.54; 95% CI, 1.01-2.34]; ≥5 vs 1-2 [HR, 2.86; 95% CI, 1.99-4.11]) were associated with DSS. Similar results were found for LRC and overall survival. More than 90% of the population was categorized as TNM stage IV, with 32% attributable to ENE. In the ENE-positive subset (n = 860), DSS ranged from 8% to 88% based on stratification using other clinicopathological factors. Conclusions and Relevance: The study results suggest that immunosuppression, perineural invasion, ENE, and size and number of nodal metastases are associated with reduced survival and LRC in HNcSCC with nodal metastases. The inclusion of ENE in HNcSCC staging needs to be reassessed, as it ascribes excessive importance to ENE and upstages most patients to TNM stage IV, despite many having a high chance of cure.

Jaw in a day surgery: early experience with 19 patients at an Australian tertiary referral center.

BACKGROUND: The Jaw-in-a-Day (JIAD) procedure aims to achieve immediate functional occlusion via a single-stage approach to maxillofacial reconstruction. While JIAD has gained popularity since its inception by Levine and colleagues, efficacy and outcome data remain limited. In this report, we discuss our experience with the JIAD technique at an Australian tertiary referral centre. METHODS: A retrospective review of all JIAD procedures performed from April 2022 to December 2023 was conducted. Clinicopathologic data reviewed included demographic information, primary diagnosis, anatomical site of disease, and history of pre-operative radiotherapy. Outcome measures of interest included operative time, number of implants placed, post-operative complications and implant survival. RESULTS: Nineteen patients were identified for the study. Two maxillary and 17 mandibular JIAD procedures were performed. The most common indications were squamous cell carcinoma (n = 8) and ameloblastoma (n = 5). Surgical complications included recipient site wound infection (n = 3), flap dehiscence (n = 2), haematoma formation (n = 1), and neck abscess associated with partial flap failure (n = 1). No total flap failures were identified. Of the 55 total implants placed, one implant failure occurred 2-months post-operatively. No loss of irradiated implants (n = 21) was observed. The median time to adjuvant radiotherapy was 57 days (range, 32-61). Eighteen of 19 patients (95%) achieved immediate dental rehabilitation, and 15/19 patients (79%) retained a functional prosthesis by the end of the follow-up period. CONCLUSIONS: Our series supports the feasibility of single-stage reconstruction for both benign and malignant indications. Further research is required to understand the long-term functional, aesthetic, and health-related quality-of-life outcomes with the JIAD technique.

Prognostic and predictive biomarkers in head and neck cancer: something old, something new, something borrowed, something blue and a sixpence in your shoe.

A biomarker is a measurable indicator of biological or pathological processes or the response to an exposure or intervention and is used to guide management decisions. In head and neck pathology, biomarkers are assessed by histological criteria and immunohistochemical and molecular studies. Surgical resection remains the mainstay of management of many head and neck malignancies. Adjuvant radiotherapy and/or systemic therapy may be administered depending on the presence of adverse prognostic factors identified on histopathological or immunohistochemical examination. In this review, we outline the clinically relevant prognostic and predictive factors in head and neck malignancies including conventionally recognised factors such as tumour size, depth of invasion, lymphovascular and perineural invasion and margin status as well as novel evolving factors such as recurrent genetic rearrangements and assessment of immune checkpoints. Practical issues are discussed to assist with recognising and reporting of these factors. A summary of useful tools such as structured pathology report formats is also included to assist with comprehensive reporting of all clinically relevant parameters, minimise risk and improve workflow efficiencies.

Predictors of distant metastatic recurrence in head and neck cutaneous squamous cell carcinoma with lymph node metastases treated with curative intent: A multicenter study.

BACKGROUND: We aimed to identify predictors of distant metastatic recurrence (DMR) in patients with head and neck cutaneous squamous cell carcinoma (HNcSCC) with nodal metastases treated with curative intent. METHODS: Predictors of DMR were identified using Cox regression in a multicenter study of 1151 patients. RESULTS: The 5-year risk of DMR was 9.6%. On multivariate analysis, immunosuppression (HR 2.93; 95% CI: 1.70-5.05; p < 0.001), nodal size >6 cm [versus ≤3 cm (HR 2.77; 95% CI: 1.09-7.03; p = 0.032)], ≥5 nodal metastases [versus 1-2 (HR 2.79; 95% CI: 1.63-4.78; p < 0.001)], and bilateral disease (HR 3.11; 95% CI: 1.40-6.90; p = 0.005) predicted DMR. A DMR risk score was developed that stratified risk from 6.6% (no risk factors) to 100% (≥3 risk factors) (p < 0.001). CONCLUSIONS: The risk of DMR in nodal metastatic HNcSCC increases with immunosuppression, nodal size >6 cm, ≥5 nodal metastases, and bilateral disease. A simple DMR risk score estimated prior to treatment may be clinically useful.