The Utility of Oncology Information Systems for Prognostic Modelling in Head and Neck Cancer.

Cancer centres rely on electronic information in oncology information systems (OIS) to guide patient care. We investigated the completeness and accuracy of routinely collected head and neck cancer (HNC) data sourced from an OIS for suitability in prognostic modelling and other research. Three hundred and fifty-three adults diagnosed from 2000 to 2017 with head and neck squamous cell carcinoma, treated with radiotherapy, were eligible. Thirteen clinically relevant variables in HNC prognosis were extracted from a single-centre OIS and compared to that compiled separately in a research dataset. These two datasets were compared for agreement using Cohen's kappa coefficient for categorical variables, and intraclass correlation coefficients for continuous variables. Research data was 96% complete compared to 84% for OIS data. Agreement was perfect for gender (κ = 1.000), high for age (κ = 0.993), site (κ = 0.992), T (κ = 0.851) and N (κ = 0.812) stage, radiotherapy dose (κ = 0.889), fractions (κ = 0.856), and duration (κ = 0.818), and chemotherapy treatment (κ = 0.871), substantial for overall stage (κ = 0.791) and vital status (κ = 0.689), moderate for grade (κ = 0.547), and poor for performance status (κ = 0.110). Thirty-one other variables were poorly captured and could not be statistically compared. Documentation of clinical information within the OIS for HNC patients is routine practice; however, OIS data was less correct and complete than data collected for research purposes. Substandard collection of routine data may hinder advancements in patient care. Improved data entry, integration with clinical activities and workflows, system usability, data dictionaries, and training are necessary for OIS data to generate robust research. Data mining from clinical documents may supplement structured data collection.

The use of alternate vertebral levels to L3 in computed tomography scans for skeletal muscle mass evaluation and sarcopenia assessment in patients with cancer: a systematic review.

Body composition measurement using diagnostic computed tomography (CT) scans has emerged as a method to assess sarcopenia (low muscle mass) in oncology patients. Assessment of skeletal muscle mass (SMM) using the cross-sectional area of a single vertebral slice (at lumbar L3) in a CT scan is correlated with whole-body skeletal muscle volume. This method is used to assess CT-defined sarcopenia in patients with cancer, with low SMM effecting outcomes. However, as diagnostic scans are based on tumour location, not all include L3. We evaluated the evidence for the use of alternate vertebral CT slices for SMM evaluation when L3 is not available. Five electronic databases were searched from January 1996 to April 2020 for studies using CT scan vertebral slices above L3 for SM measurement in adults with cancer (solid tumours). Validation with whole-body SMM, rationale for the chosen slice and sarcopenia cut-off values were investigated. Thirty-two studies were included, all retrospective and cross-sectional in design. Cervical, thoracic and lumbar slices were used (from C3 to L1), with no validation of whole-body SMM using CT scans. Alternate slices were used in lung, and head and neck cancer patients. Sarcopenia cut-off values were reported in 75 % of studies, with differing methods, with or without sex-specific values, and a lack of consensus. Current evidence is inadequate to provide definitive recommendations for alternate vertebral slice use for SMM evaluation in cancer patients. Variation in sarcopenia cut-offs warrants more robust investigation, in order for risk stratification to be applied to all patients with cancer.

The Impact of Critical Weight Loss and Reactive Feeding Tubes on Cancer-Specific Survival in Head and Neck Cancer.

Critical weight loss (CWL) continues to be a major issue in head and neck cancer (HNC) and many patients require tube feeding. We investigated the use of reactive feeding tubes (RFTs), associated CWL, and the impact on cancer-specific survival (CSS). A single-institution, retrospective audit was conducted on 460 adult HNC patients who received radiotherapy ± chemotherapy between 2005 and 2017. CSS in patients with CWL and RFTs was compared to those with no tube. Prediction analysis for RFT insertion was also performed. CWL occurred in 53% of patients, and in 88% of those with a RFT (p < 0.001). In patients with CWL, those with a RFT had worse 5 and 10-year CSS compared to those with no tube (68% and 65% vs 83% and 80% respectively, p = 0.040) in multivariate Cox regression analysis. Concurrent chemoradiotherapy combined with CWL was the strongest predictor for RFT insertion (p = 0.003). CWL, combined with having a RFT, impacts negatively on CSS. CWL may be one of the triggers for RFT insertion, however those with no tube have better CSS. This may be due to higher weight loss levels seen in those who have a RFT, and earlier insertion to prevent such losses seems indicated.

Content analysis of rehabilitation goals for patients following non-surgical head and neck cancer treatment.

PURPOSE: Following head and neck cancer (HNC) treatment, individuals experience an array of side effects which can impact on physical, emotional, and practical aspects of their lives. Responsive, supportive rehabilitation services are therefore essential to address ongoing survivorship needs. This study examined the nature of patient-reported goals from acute to long-term post-treatment, to inform design/delivery of future rehabilitation services. METHODS: Using a cross-sectional cohort design, 91 patients between 2 weeks and 5 years of post non-surgical HNC treatment (acute n = 29; sub-acute n = 28; long-term n = 34), provided their top four rehabilitation goals considering any aspect of their lives. Content analysis was used to categorise responses at each time point. RESULTS: Three core categories of patient goals were identified relating to: (1) treatment side effects (TSE), (2) overall health (OH), and (3) living life (LL). TSE goals were a priority during the acute and sub-acute phases, with less focus long-term. LL goals were prevalent across all time points, though increased in the long-term. Approximately a third of all goals at each time point related to OH. CONCLUSIONS: A variety of rehabilitation goals were identified, and the focus shifted over time. These data highlight the importance of changing the focus of rehabilitation as patients' priorities vary over time. Early multidisciplinary care from allied health services is crucial to provide support with managing side effects and returning to daily activities. In the long-term, greater input from services to address health, nutrition, leisure, and fitness goals may be more beneficial.

Optimising Radiation Therapy Dose to the Swallowing Organs at Risk: An In Silico Study of feasibility for Patients with Oropharyngeal Tumours.

Recent evidence suggests that reducing radiotherapy dose delivered to specific anatomical swallowing structures [Swallowing Organs at Risk (SWOARs)] may improve swallowing outcomes post-treatment for patients with head and neck cancer. However, for those patients with tumours of the oropharynx, which typically directly overlap the SWOARs, reducing dose to these structures may be unachievable without compromising on the treatment of the disease. To assess the feasibility of dose reduction in this cohort, standard IMRT plans (ST-IMRT) and plans with reduced dose to the SWOARs (SW-IMRT) were generated for 25 oropharyngeal cancer patients (Brouwer et al. in Radiother Oncol 117(1):83-90, https://doi.org/10.1016/j.radonc.2015.07.041 , 2015; Christianen et al. in Radiother Oncol 101(3):394-402, https://doi.org/10.1016/j.radonc.2011.05.015 , 2011). ST-IMRT and SW-IMRT plans were compared for: mean dose to the SWOARs, volume of pharynx and larynx receiving 50 Gy and 60 Gy (V50 and V60 respectively) and overlap between the tumour volume and the SWOARs. Additionally, two different SWOARs delineation guidelines (Brouwer et al. in Radiother Oncol 117(1):83-90, https://doi.org/10.1016/j.radonc.2015.07.041 , 2015; Christianen et al. in Radiother Oncol 101(3):394-402, https://doi.org/10.1016/j.radonc.2011.05.015 , 2011) were used to highlight differences in calculated volumes between existing contouring guidelines. Agreement in SWOARs volumes between the two guidelines was calculated using a concordance index (CI). Despite a large overlap between the tumour and SWOARs, significant (p < 0.05) reductions in mean dose to 4 of the 5 SWOARs, and V50/V60 for the pharynx and larynx were achieved with SW-IMRT plans. Low CIs per structure (0.15-0.45) were found between the two guidelines highlighting issues comparing data between studies when different guidelines have been used (Hawkins et al. in Semin Radiat Oncol 28(1):46-52, https://doi.org/10.1016/j.semradonc.2017.08.002 , 2018; Brodin et al. in Int J Radiat Oncol Biol Phys 100(2):391-407, https://doi.org/10.1016/j.ijrobp.2017.09.041 , 2018). This study found reducing dose to the SWOARs is a feasible practice for patients with oropharyngeal cancer. However, future prospective research is needed to determine if the extent of dose reduction achieved equates to clinical benefits.

Treatment toxicities and their impact on oral intake following non-surgical management for head and neck cancer: a 3-year longitudinal study.

PURPOSE: Patients who receive (chemo)radiotherapy [(C)RT] for head and neck cancer (HNC) experience multiple treatment effects. However, the presence and recovery of treatment toxicities and how these impact on oral intake over time post-treatment are not fully understood. The primary aim of this study was to examine patient perceptions of the toxicities present and which are barriers to oral intake, up to 3 years post (C)RT. The secondary aim was to identify mealtime strategies used to optimise oral intake. METHODS: A prospective cohort of 96 patients after completion of (C)RT for HNC reported the presence of toxicities, if they were barriers to oral intake, and use of any mealtime strategies at the end of treatment (EoT), and at 3, 6, 12, 24, and 36 months post-treatment. RESULTS: All toxicities and reported barriers changed over time (p < 0.05) except trismus. Odynophagia, reduced appetite, and fatigue improved (p < 0.05) by 3 months. Significantly less patients reported xerostomia and dysgeusia as barriers to oral intake at 3 months despite no improvement in their presence. No change in the presence of any toxicity or its impact on oral intake occurred from 12 to 36 months, with exception of dentition problems which significantly increased at 36 months. Alternating food/fluids was the most frequently used mealtime swallowing strategy at all time points beyond the EoT. CONCLUSIONS: The dysphagia and associated toxicities HNC patients experience are chronic in nature. Rehabilitation should include mealtime strategies and support with adjusting to the changing presence and impact of toxicities on oral intake.

Critical Weight Loss in Patients With Oropharynx Cancer During Radiotherapy (± Chemotherapy).

Critical weight loss (CWL) defined as ≥5% in one month, is common in patients with oropharynx cancer and identification of patients at risk is challenging. We aimed to investigate if predictors of CWL in this population exist to guide nutritional intervention. Data were collected retrospectively on 134 patients who had radiotherapy (RT) ± concurrent chemotherapy (CRT) ± surgery. Body weights were collected pre-RT and during RT, with percentage weight change measured against baseline. Logistic regression was used to analyze chosen predictors. The incidence of CWL was 67% (26% of these patients experiencing ≥10% loss). Patients who had CRT experienced significantly higher weight loss (7.1% versus 4.7%; p = 0.001). Tube feeding was used in 64% of patients with CWL, the majority of tubes inserted reactively. These patients had a mean weight change of -8.8% (versus -7.1% in those with no tube) (p = 0.004). Multivariate models identified increased risk of CWL in tonsil origin tumors (p < 0.05), with CRT being the only predictor of weight loss ≥10% (p < 0.05). These patients are particularly vulnerable to CWL and the majority experience significant nutritional issues during RT, regardless of nutritional status at diagnosis. Nutritional intervention should be targeted accordingly.

Clinical predictors for reactive tube feeding in patients with advanced oropharynx cancer receiving radiotherapy ± chemotherapy.

Enteral feeding is often required for nutrition support in head and neck cancer patients when oral intake is inadequate. When to initiate the insertion of a feeding tube continues to be a debated issue in our institution. We investigated the use of reactive feeding tubes (RFTs) in patients with advanced stage oropharynx cancer (OPC). Data were retrospectively collected on 131 patients who had radiotherapy (RT) ± chemotherapy from 2005 to 2015. Predictors for RFT insertion were investigated. Weight loss during RT was compared between those with RFT versus prophylactic tubes (PFTs) versus no tube, and survival outcomes evaluated. RFTs were more likely to be needed in patients who had bilateral neck node irradiation (p = 0.001) and concurrent chemoradiotherapy (CRT) (p = 0.038). Patients with RFTs had significantly higher mean percentage weight loss during RT (9.5 ± 3.4%) (p < 0.001) when compared to those with a PFT (5.2 ± 4.7%) and those with no tube (5.4 ± 3.1%). No difference was seen in 5-year survival rates in patients who did not have a feeding tube to those who required a RFT. RFT use is frequent in OPC, although difficult to predict. CRT and bilateral neck node irradiation were found to be associated with the need for the insertion of a feeding tube during RT. These patients also experience significantly higher weight loss, therefore, prophylactic tubes may need to be considered more often in this population.

Pretreatment factors associated with functional oral intake and feeding tube use at 1 and 6 months post-radiotherapy (+/- chemotherapy) for head and neck cancer.

A proportion of patients with head and neck cancer (HNC) experience significant swallowing difficulty during and post-radiotherapy/chemoradiotherapy (RT/CRT). Identifying patients during the pretreatment period who are anticipated to have compromised oral intake would allow for early and accurate patient education, and prioritisation of their management. Ascertaining a clear set of pretreatment predictors from the literature is challenging due to heterogeneity in study designs and patient cohorts, with minimal prospective data available (especially at 1-month post-treatment). The objectives of this study were to investigate which pretreatment factors predicted compromised oral intake and feeding tube use at 1 and 6 months post-RT/CRT. Prospective data were collected on 80 consecutive HNC patients receiving RT/CRT from 2011 to 2014. The primary outcome was to identify predictors of a modified diet at 1 and 6 months post-RT/CRT. Secondary outcomes were to identify predictors of feeding tube use at these time intervals, and <6 vs. >6 week duration of feeding tube use. Multivariate analysis revealed bilateral neck radiotherapy treatment was a strong predictor of modified diets at 1 month (p < 0.001), and T-stages T3/T4 a predictor of modified diets at 6 months (p = 0.03). Patients treated with concurrent CRT (p = 0.02) and bilateral neck treatment (p = 0.02) predicted feeding tube use at 1 month, and concurrent CRT predicted feeding tube use for >6 weeks (p = 0.04). Therefore, patients receiving bilateral neck treatment and/or CRT are at greatest risk of requiring modified diets and feeding tube use early post-treatment, and should be prioritised for intervention and ongoing support.

Acceptance and commitment therapy program for distressed adults with a primary brain tumor: a case series study.

Research has indicated that adults diagnosed with a primary brain tumor (BT) are susceptible to experiencing anxiety and depressive problems post-diagnosis. However, there is a notable paucity of psychological interventions which have been tested with adult BT patients. An acceptance and commitment therapy (ACT)-based manualized program was developed for anxious and/or depressed BT patients. The preliminary efficacy of this program was initially tested using a proof-of-concept study design based on a case series of four clinically distressed BT patients. Three of the four participants no longer met criteria for anxiety and/or depressive disorders at post-therapy, and these effects were maintained at 3 months of follow-up. The fourth participant, who had a premorbid psychiatric history, experienced a stabilization of anxiety and depressive symptoms. Given the current dearth of studies which have tested psychological interventions for distressed BT survivors, these preliminary findings have promising clinical utility. However, the efficacy of psychological interventions tailored for clinically distressed BT patients needs to be further tested using larger-scale controlled trial designs.

Successful "medical" orbital decompression with adjunctive rituximab for severe visual loss in IgG4-related orbital inflammatory disease with orbital myositis.

IgG4-related disease (IgG4-RD) is an inflammatory condition of unknown etiology that can cause tumefactive lesions in a number of tissues and organs, including the orbit and ocular adnexa. Diagnostic criteria for IgG4-RD, including pathology and clinical features and pathology, have been recently proposed. This study presents the first case of unilateral acute visual loss secondary to IgG4-related orbital inflammatory disease with orbital myositis that was complicated by severe compressive optic neuropathy. After initial treatment with pulsed intravenous methylprednisolone, followed by rituximab and radiotherapy, there was a marked improvement in orbital inflammation and clinical and radiological improvement in the compressive optic neuropathy. After 9 months of follow up, the orbital inflammatory disease remained in remission.

Implementing flexible endoscopic evaluation of swallow screening within annual cancer surveillance appointments to monitor for late-stage radiation-induced dysphagia: A feasibility study.

BACKGROUND: Late-stage progressive decline of swallowing function after radiotherapy for head and neck cancer (HNC) is often difficult to monitor. This study examined the feasibility and clinical outcomes of speech-language pathology implementing flexible endoscopic evaluation of swallow (FEES) screening during annual cancer surveillance visits to monitor late-stage swallowing function. METHODS: Patients >2 years post treatment who attended routine oncological visits underwent FEES screening. Feasibility (service data, stakeholder survey) and swallowing outcomes (oral intake, secretions, internal lymphedema, penetration-aspiration, and residue) were collected. RESULTS: Screening was completed with 70% (50/71) of eligible patients. Medical staff and speech-language pathologists indicated the protocol was worthwhile and achievable to incorporate into practice. Almost all patients were willing to complete the protocol annually. FEES outcomes identified 84% with dysphagia versus only 26% self-reported dysphagia. CONCLUSION: Findings indicate FEES screening incorporated into annual oncological reviews is feasible and effective at monitoring late-stage swallowing function following HNC.

Improving accuracy in nodal staging of oral cancer: Proposal of a new system.

BACKGROUND: Despite introduction of extranodal extension (ENE) into the AJCC 8th edition of oral cancer staging, previous criticisms persist, such as limited discrimination between sub-stages and doubtful prognostic value of contralateral nodal disease. The purpose of this study was to compare our novel nodal staging system, based on the number of positive nodes and ENE, to the AJCC staging system in surgically treated patients. METHODS: Retrospective analysis of 4710 patients with oral squamous cell carcinoma (OSCC) treated with surgery±adjuvant therapy in 8 institutions in Australia, North America and Asia. With overall survival (OS) and disease specific survival (DSS) as endpoint, the prognostic performance of AJCC 8th and 7th editions were compared using hazard consistency, hazard discrimination, likelihood difference and balance. RESULTS: Our new nodal staging system (PN) a progressive and linear increase in hazard ratio (HR) from pN0 to pN3, with good separation of Kaplan Meier curves. Using the predetermined criteria for evaluation of a staging system, our proposed staging model outperformed AJCC 8th and 7th editions in prediction of OS and DSS. CONCLUSION: PN was the lymph node staging system that provided the most accurate prediction of OS and DSS for patients in our cohort of OSCC. Additionally, it can be easily adopted, addresses the shortcomings of the existing systems and should be considered for future editions of the TNM staging system.

Empirical comparison of routinely collected electronic health record data for head and neck cancer-specific survival in machine-learnt prognostic models.

BACKGROUND: Knowledge of the prognostic factors and performance of machine learning predictive models for 2-year cancer-specific survival (CSS) is limited in the head and neck cancer (HNC) population. METHODS: Data from our facilities' oncology information system (OIS) collected for routine practice (OIS dataset, n = 430 patients) and research purposes (research dataset, n = 529 patients) were extracted on adults diagnosed between 2000 and 2017 with squamous cell carcinoma of the head and neck. RESULTS: Machine learning demonstrated excellent performance (area under the curve, AUC) in the whole cohort (AUC = 0.97, research dataset), larynx cohort (AUC = 0.98, both datasets), and oropharynx cohort (AUC = 0.99, both datasets). Tumor site and T classification were identified as predictors of 2-year CSS in both datasets. Hypothyroidism and fitness for operation were further identified in the research dataset. CONCLUSIONS: Datasets extracted from an OIS for routine clinical practice and research purposes demonstrated high utility for informing 2-year head and neck CSS.

Inter-hospital variation in data collection, radiotherapy treatment, and survival in patients with head and neck cancer: A multisite study.

BACKGROUND AND PURPOSE: Inter-hospital inequalities in head and neck cancer (HNC) survival may exist due to variation in radiotherapy treatment-related factors. This study investigated inter-hospital variation in data collection, primary radiotherapy treatment, and survival in HNC patients from an Australian setting. MATERIALS AND METHODS: Data collected in oncology information systems (OIS) from seven Australian hospitals was extracted for 3,182 adults treated with curative radiotherapy, with or without surgery or chemotherapy, for primary, non-metastatic squamous cell carcinoma of the head and neck (2000-2017). Death data was sourced from the National Death Index using record linkage. Multivariable Cox regression was used to assess the association between survival and hospital. RESULTS: Inter-hospital variation in data collection, primary radiotherapy dose, and five-year HNC-related death was detected. Completion of eleven fields ranged from 66%-98%. Primary radiotherapy treated Tis-T1N0 glottic and any stage oral cavity and oropharynx cancers received significantly different time-corrected biologically equivalent dose in two gray fractions (EQD2T) by hospital, with observed deviation from Australian radiotherapy guidelines. Increased EQD2T dose was associated with a reduced risk of five-year HNC-related death in all patients and those treated with primary radiotherapy. Hospital, tumour site, and T and N classification were also identified as independent prognostic factors for five-year HNC-related death in all patients treated with radiotherapy. CONCLUSION: Unexplained variation exists in HNC-related death in patients treated at Australian hospitals. Available routinely collected data in OIS are insufficient to explain variation in survival. Innovative data collection, extraction, and classification practices are needed to inform clinical practice.

Machine Learning and Nomogram Prognostic Modeling for 2-Year Head and Neck Cancer-Specific Survival Using Electronic Health Record Data: A Multisite Study.

PURPOSE: There is limited knowledge of the prediction of 2-year cancer-specific survival (CSS) in the head and neck cancer (HNC) population. The aim of this study is to develop and validate machine learning models and a nomogram for the prediction of 2-year CSS in patients with HNC using real-world data collected by major teaching and tertiary referral hospitals in New South Wales (NSW), Australia. MATERIALS AND METHODS: Data collected in oncology information systems at multiple NSW Cancer Centres were extracted for 2,953 eligible adults diagnosed between 2000 and 2017 with squamous cell carcinoma of the head and neck. Death data were sourced from the National Death Index using record linkage. Machine learning and Cox regression/nomogram models were developed and internally validated in Python and R, respectively. RESULTS: Machine learning models demonstrated highest performance (C-index) in the larynx and nasopharynx cohorts (0.82), followed by the oropharynx (0.79) and the hypopharynx and oral cavity cohorts (0.73). In the whole HNC population, C-indexes of 0.79 and 0.70 and Brier scores of 0.10 and 0.27 were reported for the machine learning and nomogram model, respectively. Cox regression analysis identified age, T and N classification, and time-corrected biologic equivalent dose in two gray fractions as independent prognostic factors for 2-year CSS. N classification was the most important feature used for prediction in the machine learning model followed by age. CONCLUSION: Machine learning and nomogram analysis predicted 2-year CSS with high performance using routinely collected and complete clinical information extracted from oncology information systems. These models function as visual decision-making tools to guide radiotherapy treatment decisions and provide insight into the prediction of survival outcomes in patients with HNC.

Evaluation of an automated Presidio anonymisation model for unstructured radiation oncology electronic medical records in an Australian setting.

BACKGROUND: Electronic medical records (EMRs) contain valuable information for clinical research, however, the presence of personally identifying information (PII) restricts their use. Anonymisation of PII from EMRs enables clinical information to be shared for research purposes. Since there is limited research relating to the anonymisation of Australian EMRs, the performance of Microsoft Presidio with customisation on clinical documents from an Australian radiation oncology information system (OIS) was evaluated. METHODS: A random sample of 300 unstructured free-text clinical documents were extracted from the Prince of Wales Cancer Centre OIS on patients diagnosed with cancer of the head and neck between 2000 and 2017. Anonymisation of clinical text was performed using Microsoft Presidio, implemented in Python programming language. Each clinical document was manually compared pre- and post-anonymisation for the identification and redaction of 13 PII. Model performance was evaluated using three classification criteria; correct, partial, and missed classification, to determine recall, precision, and F1-score. These three metrics were performed under relaxed conditions, where partial classifications were considered correct, and under strict conditions, where only correct classifications were considered correct. RESULTS: A total of 8,713 PII were identified, of which 7,026 (81%) were classified as correct, 850 (10%) as partial, and 837 (9%) as missed. There were 245 instances of incorrect classifications. Evaluation of the model demonstrated an average precision of 0.8921, recall (strict) of 0.8064, F1-score (strict) of 0.8471, recall (relaxed) of 0.9039, and F1-score (relaxed) of 0.8980. CONCLUSION: This is the first example of an open-source anonymisation model to be customised and tested on clinical documents from an Australian radiation oncology EMR. These findings support the use of Presidio for the safe use and sharing of cancer data within Australia for certain PII, however, additional checks are required to ensure person names are successfully anonymised.

Outcomes of patients with metastatic cutaneous squamous cell carcinoma to the axilla: a multicentre cohort study.

BACKGROUND: Metastatic cutaneous squamous cell carcinoma to the axilla is uncommon, with limited data to guide management. We sought to assess the outcomes of patients with this condition after surgery and radiotherapy. METHODS: A retrospective cohort study of patients treated at two Australian hospitals from 1994 through 2016 was performed. RESULTS: A total of 74 patients were identified, including 48 treated curatively with surgery-plus-radiotherapy and 15 with surgery alone. Compared with patients treated with surgery alone, a higher proportion of patients treated with surgery-plus-radiotherapy had lymph nodes larger than 6 cm (53% versus 8%, P = 0.012) and multiple adverse histopathological features (75% versus 47%, P = 0.04). The groups had similar 5-year disease-free survival (45% versus 46%) and overall survival (51% versus 48%). Presence of multiple positive lymph nodes was associated with reduced disease-free survival (hazard ratio 4.57, P = 0.01) and overall survival (hazard ratio 3.53, P = 0.02). Regional recurrence was higher in patients treated with surgery alone (38% versus 22%, P = 0.22) and patients with lymph nodes larger than 6 cm (34% versus 10%, P = 0.03). All recurrences occurred within 2 years following treatment. CONCLUSION: Combined-modality therapy for metastatic cutaneous squamous cell carcinoma to the axilla is recommended for high-risk patients, although outcomes remain modest. The key period for recurrence is within 2 years following treatment.

Geographical heterogeneity in the American Joint committee on Cancer oral cancer staging and prognostic implications.

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 that determine the impact on prognostic heterogeneity. MATERIALS AND METHODS: Retrospective analysis of 4710 patients with oral squamous cell carcinoma (OSCC) treated with surgery +/- adjuvant therapy in 8 institutions in Australia, North America and Asia. With overall survival (OS) as endpoint, the prognostic performance of AJCC 7th and 8th editions were compared using Akaike Information Criterion (AIC), Bayesian Information Criteria (BIC), Harrell's concordance index (C-index). RESULTS: When comparing AJCC 8 to AJCC 7, the heterogeneity in prediction of OS increased for T-category and N-category while remaining unchanged for TNM staging, suggesting AJCC 8 increased complexity with no improvement in predictive value. There were significant differences in median DOI and incidence of ENE between geographical regions, resulting in dissimilar rates of stage-migration when adopting AJCC 8. CONCLUSION: In an attempt to improve prognostic performance, AJCC 8 introduced more variables; however heterogeneity in these results in significant geographical differences in model discrimination and performance. Caution should be applied as this may result in inaccurate and unreliable prognostic predictions that may impact treatment recommendations.

The incidence of squamous cell carcinoma of the oral tongue is rising in young non-smoking women: An international multi-institutional analysis.

PURPOSE: Increasing evidence is accumulating for an alarming rising incidence of oral tongue SCC in a younger cohort, particularly in developed countries. The aim of this study is to analyse the change in incidence of OSCC in patients under the age of 45 in developed nations in the Asia-Pacific region. PATIENTS AND METHODS: Population data was extracted from the Australian Cancer Incidence and Mortality 2017 database and National Registry of Diseases Office, Singapore to allow calculation of the incidence in the Australian and Singaporean populations. This was compared to multi-institutional data from four tertiary Australian institutions. The inclusion criteria were as follows: a) diagnosis of primary SCC of the mobile tongue; b) treatment with curative intent; c) complete histopathologic data; d) complete adjuvant treatment data; e) follow up data. RESULTS: Analysis of ACIM data demonstrated that there was a significant increase in the incidence of tongue SCC in those under the age of 45 in the Australian and Singaporean populations (p < 0.001). When analysed for gender, the incidence of tongue SCC increased at a significantly higher rate in females than males (p < 0.001). Similarly, in the multi-institutional analysis including 1814 patients, the number of females under the age of 45 with tongue SCC significantly increased over time (p < 0.001), with the proportion of smokers in this cohort decreasing over time. CONCLUSION: The incidence of tongue SCC is rising in young females in developed nations in the Asia Pacific region, in keeping with observed epidemiological trends worldwide.