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Background: Keratinocyte cancer (KC) in Australia poses a unique healthcare challenge due to its high prevalence and the requirement for multidisciplinary management of many cases. Advances in radiation therapy (RT) have increased its use in treating different keratinocyte cancer presentations. Understanding the indications for RT and the role that general practitioners (GPs) play in the treatment pathway are imperative to ensure best patient outcomes., Objective: This review examined the efficacy, advances and treatment considerations of RT for the management of keratinocyte cancer, and role of the GP in the treatment pathway., Discussion: Radiation therapy offers effective alternatives to, or adjuvants for, surgery in existing keratinocyte cancer treatments in appropriate cases. The evolving RT landscape necessitates GPs to be well informed for effective case identification, referral and management. This includes understanding RT advances, protocols, treatment reactions and managing patient expectations. Continuing education in this space is important for GPs to understand the suitability of RT for their patients.

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., (© 2024 The Author(s). ANZ Journal of Surgery published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Surgeons.)

Background: There are no large studies reporting oncological or survival outcomes for patients diagnosed with perineural spread (PNS) of cutaneous squamous cell carcinoma (cSCC) via the ophthalmic nerve (V 1 ). Where orbital exenteration may be necessary for curative treatment, it is critical to have survival data with which the morbidity associated with surgical treatment can be justified. Furthermore, with the emerging treatment option of immunotherapy, current standard of care outcomes are needed to help guide future trial design and eventually changed management guidelines., Objective: To determine the oncological and survival outcomes observed in patients with PNS of cSCC via V 1 ., Materials and Methods: Retrospective analysis of prospectively maintained cohort of patients with PNS of cSCC via V1 treated in a tertiary Australian head and neck oncology/skull base referral center. Consecutive sample of 53 patients managed between March 1, 1999 and April 30, 2020. Follow-up closure date was September 1, 2021. Curative-intent surgery, curative-intent radiotherapy, or palliative care was undertaken. Endpoints included five-year overall, disease-specific, and disease-free survival from the date of treatment., Results: Five-year Kaplan-Meier overall survival was 61.9% (95% CI 46.2%-74.3%), with disease-specific survival of 74.6% (95% CI 58.8%-85.3%), and disease-free survival 62.1% (95% CI 46.5%-74.3%). Survival was superior in patients treated via surgery and adjuvant radiotherapy than in those receiving surgery alone or definitive radiotherapy. Survival was superior among patients with less advanced disease as assessed by the Williams zonal staging system; patients with Zone 1 disease had disease-specific survival of 94.1% at 5 years with 82.5% disease-free survival., Discussion: Five-year oncological and survival outcomes in this cohort were favorable. Superior survival was observed in patients treated with curative-intent surgery and adjuvant radiotherapy. Less extensive disease as delineated by the Williams zonal staging system was associated with improved survival., Conclusion: Surgical resection with adjuvant radiotherapy confers favourable oncological and survival outcome in patients with V1 PNS, particularly with early disease limited to Zone 1., (© 2024 The Author(s). Head & Neck published by Wiley Periodicals LLC.)

Deaths from non-melanoma skin cancers (NMSCs) have almost doubled in Australia in recent years. Cutaneous squamous cell carcinoma (cSCC) constitutes approximately 20% of NMSCs, but is responsible for most of the deaths. Most skin cancers are easy to diagnose and treat and therefore cSCC are often trivialised; however, there is a high-risk subgroup of cSCC (HRcSCC) that is associated with a high risk of metastasis and death. The definition of early HRcSCC and our ability to identify them is evolving. Many significant prognostic factors have been identified, but a universally accepted prognostic index does not exist. Guidelines for workup, treatment, and follow-up leave many important decisions open to broad interpretation by the treating physician or multidisciplinary team. Some of the treatments used for metastatic cSCC are not supported by robust evidence and the prognosis of metastatic cSCC is guarded. In this review, we highlight the rapid rise in NMSC deaths and discuss some of the deficiencies in our knowledge of how to define, diagnose, stage, and manage HRcSCC., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

We present a cohort review of TORS resection for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) and its associated oncological outcomes spanning a 10-year period. A retrospective case series review was performed of patients undergoing primary surgical treatment for HPV-associated OPSCC through the St. Vincent's Head and Neck Cancer service from 2011 to 2022. The primary outcomes were to investigate complete resection of the primary tumour, rates of recurrence, and survival analysis. Secondary outcomes included complications, rates of adjuvant therapy, sites of recurrence and rates of percutaneous endoscopic gastrostomy (PEG). 184 patients underwent TORS-based therapy with neck dissection, and guideline-directed adjuvant therapy for HPV-associated OPSCC. Our median follow-up was 46 months. The positive margin rate on final histopathology analysis was 10.9%. Adjuvant therapy was indicated in 85 patients (46%). The local recurrence rate was 10.9% with the majority (80%) of patients recurring in the first 3 years since treatment. The disease-specific survival at 3 years was 98.6% and at 5 years was 94.4%. The 3-year and 5-year OS for the cohort was 96.7% and 92.5%, respectively. The presence of extranodal extension and positive margins were associated with increased risk of recurrence, whereas adjuvant therapy was found to be a protective factor for both overall recurrence and survival. Major complications occurred in 12 patients (6.5%), resulting in one death. This study has demonstrated that primary surgical therapy for HPV-associated OPSCC is a safe and effective treatment modality with low local recurrence and complication rates, and overall survival benefits., (© 2024. Crown.)

Objectives: To examine recent changes in the numbers of Medicare-subsidised keratinocyte cancer excisions, particularly for younger people exposed to primary prevention campaigns since the early 1980s., Study Design: Retrospective cohort study; analysis of administrative data., Setting, Participants: Analysis of Medicare Benefits Schedule (MBS) claims data for procedures related to the diagnosis and treatment of keratinocyte cancer in Australia, 2012-2021., Main Outcome Measures: Age-standardised rates for MBS-subsidised claims for first surgical squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) excisions, Mohs surgery, surgical excisions of benign lesions, skin biopsies, and cryotherapy or serial curettage of premalignant and malignant lesions, overall, and by sex, state/territory, and age group; average annual percentage change in rate for time intervals determined by joinpoint regression., Results: In men, the age-standardised rate of BCC/SCC excisions increased by 1.9% (95% confidence interval [CI], 1.4-2.4%) per year during 2012-2019 (from 2931 to 3371 per 100 000 men) and then declined by 3.8% (95% CI, 0.5-7.0%) per year during 2019-2021 (to 3152 per 100 000). In women, the age-standardised rate increased by 2.2% (95% CI, 1.7-2.8%) per year during 2012-2019 (from 1798 to 2093 per 100 000 women); the decline to 1967 excisions per 100 000 women in 2021 was not statistically significant. BCC/SCC excision rates declined for men under 55 years of age (by 1.0-3.4% per year) and women under 45 years of age (by 1.7-2.3% per year). Age-standardised biopsy rates increased during 2012-2021 in all age groups (by 2.8-6.9% per year)., Conclusions: Rates of MBS-subsidised treatment for keratinocyte cancers increased during 2012-2019, but BCC/SCC treatment rates declined among younger Australians, who have probably been exposed to less sunlight than earlier generations because of public health interventions and population-wide lifestyle changes related to technology use., (© 2024 The Authors. Medical Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of AMPCo Pty Ltd.)

Introduction: Concurrent chemoradiotherapy is the standard of care in the curative intent treatment of squamous cell carcinoma (SCC) of the anus. Volumetric arc therapy (VMAT) is a highly conformal radiation therapy technique that has been implemented to reduce toxicity for these patients. However, there are few reports evaluating the long-term outcomes of VMAT. Thus, we evaluated the survival and toxicity outcomes of anal cancer patients treated in our regional cancer centre undergoing curative intent chemoradiotherapy using VMAT and following the Australian EviQ guidelines., Methods: All consecutive patients treated with the VMAT technique for curative-intent definitive chemoradiotherapy for anal SCC at our institution from 2013 until 2022 were retrospectively reviewed for survival and toxicity outcomes. Kaplan-Meier estimates of locoregional control, distant metastasis-free survival, disease-free survival, anal cancer-specific survival and overall survival were obtained., Results: In total, 44 patients were analysed. The median follow-up was 48.9 months (Range 7.8-107). 97.7% of patients completed the prescribed radiation therapy and 88.6% chemotherapy. Five patients (11.4%) recurred. Four (9.1%) had isolated local failures, and one (2.3%) had an isolated distant failure. There were no regional nodal failures. The Kaplan-Meier estimates for locoregional control, distant metastasis-free survival, disease-free survival, anal cancer-specific survival and overall survival were 90.3%, 97.7%, 88.1%, 97.1% and 87% at 3 years, and 90.3%, 97.7%, 88.1%, 93.0% and 72.3% at 5 years, respectively. Acute grade 3 genitourinary (GU), gastrointestinal (GI) and skin toxicities occurred in 2.2%, 6.8% and 13.6% of patients, respectively. There were no acute grade 4 toxicities. Late grade 2 GU and GI toxicities occurred in 6.8% and 11.3% of patients, respectively. There were no late grade 3 or 4 toxicities or treatment-related deaths. The 5 -year colostomy-free survival rate was 86.4%., Conclusion: Outcomes for anal SCC after definitive chemoradiotherapy using VMAT in our regional cancer centre results in low rates of grade 3/4 toxicity, high rates of organ preservation and excellent survival outcomes., (© 2024 The Authors. Journal of Medical Imaging and Radiation Oncology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Radiologists.)

Background: Cutaneous squamous cell carcinoma (CSCC) has a propensity for perineural spread (PNS) which is associated with poorer treatment outcomes. Immunotherapy is the new standard of care treatment for advanced CSCC resulting in durable responses. PNS is not captured by traditional response assessment criteria used in clinical trials, e.g. RECIST 1.1, and there is limited literature documenting radiological PNS responses to immunotherapy. In this study we assess PNS responses to immunotherapy using a modified grading system., Methods: This is an Australian single-center retrospective review of patients with advanced CSCC who were treated with immunotherapy between April 2018 and February 2022 who had evidence of PNS on pre-treatment magnetic-resonance imaging (MRI). The primary outcome was blinded overall radiological response in PNS using graded radiological criteria, post-commencement of immunotherapy. Three defined timepoints (< 5 months, 5-10 months, > 10 months) were reviewed. Secondary outcomes included a correlation between RECIST 1.1 and PNS assessments and the assessment of PNS on fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT)., Results: Twenty CSCC patients treated with immunotherapy were identified. Median age was 75.7 years and 75% (n = 15) were male. All patients had locoregionally advanced disease and no distant metastases. Median follow-up was 18.5 months (range: 2-59). 70% (n = 14) demonstrated a PNS response by 5 months. Three patients experienced pseudoprogression. One patient had PNS progression by the end of study follow up. RECIST 1.1 and PNS responses were largely concordant at > 10 months (Cohen's Kappa 0.62). 5/14 cases had features suspicious for PNS on FDG-PET/CT., Conclusions: PNS response to immunotherapy can be documented on MRI using graded radiological criteria. High response rates were seen in PNS with the use of immunotherapy in this cohort and these responses were largely concordant with RECIST 1.1 assessments. FDG-PET/CT demonstrated limited sensitivity in the detection of PNS., (© 2024. The Author(s).)

The concurrent diagnoses of Buruli ulcer (BU) and cutaneous squamous cell carcinoma (SCC) is a phenomenon not previously described, despite the fact that both conditions are highly prevalent in Australia. This report presents an intriguing case of concurrent diagnoses, with clues alluding to more than one skin condition being present. The case involves a 73-year-old man with BU diagnosed on the scalp, an atypical location, which led to the consideration of malignancy, ultimately revealing concurrent SCC. This case highlights the importance of considering both conditions in patients with epidemiological risk factors, necessitating multiple lines of investigation for accurate diagnosis. Medical practitioners must remain vigilant and incorporate this possibility into their diagnostic algorithms for suspicious skin lesions to optimize treatment and outcomes. This is the first recorded instance of simultaneous diagnosis, underlining the need for enhanced awareness and attention to these unique cases., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 O’Keeffe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: To review the outcomes of immune checkpoint inhibitor (ICI) treatment of advanced cutaneous squamous cell carcinoma (CSCC) outside clinical trials., Study Design: Retrospective observational study; review of patient records in fifteen Australian institutions., Setting, Participants: All Australian adults with locally advanced or metastatic CSCC not amenable to curative surgery or radiotherapy treated with ICIs, 5 May 2017 - 23 May 2022, through a cemiplimab compassionate access scheme (Therapeutic Goods Administration Special Access Scheme) or who personally covered the cost of pembrolizumab prior to the start of the access scheme., Main Outcome Measures: Best overall response rate (ORR) according to standardised assessment criteria using the hierarchy: Response Evaluation Criteria in Solid Tumors (RECIST 1.1), the modified World Health Organization clinical response criteria, and the Positron Emission Tomography Response Criteria (PERCIST 1.0); overall and progression-free survival., Results: A total of 286 people with advanced CSCC received ICI therapy during May 2017 - May 2022 (cemiplimab, 270; pembrolizumab, 16). Their median age was 75.2 years (range, 39.3-97.5 years) and 232 were men (81%); median follow-up time was 12.2 months (interquartile range, 5.5-20.5 months). Eighty-eight people (31%) were immunocompromised, 27 had autoimmune disease, and 59 of 277 (21%) had ECOG performance scores of 2 or 3. The ORR was 60% (166 of 278 evaluable patients): complete responses were recorded for 74 (27%) and partial responses for 92 patients (33%). Twelve-month overall survival was 78% (95% confidence interval [CI], 72-83%); progression-free survival was 65% (95% CI, 58-70%). Poorer ECOG performance status was associated with poorer overall survival (per unit: adjusted hazard ratio [aHR], 3.0; 95% CI, 2.0-4.3) and progression-free survival (aHR, 2.4; 95% CI, 1.8-3.3), as was being immunocompromised (overall: aHR, 1.8; 95% CI, 1.1-3.0; progression-free: aHR, 1.8; 95% CI, 1.2-2.7). Fifty-five people (19%) reported immune-related adverse events of grade 2 or higher; there were no treatment-related deaths., Conclusion: In our retrospective study, the effectiveness and toxicity of ICI therapy were similar to those determined in clinical trials. Our findings suggest that ICIs could be effective and well tolerated by people with advanced CSCC who are ineligible for clinical trials., (© 2024 The Authors. Medical Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of AMPCo Pty Ltd.)

Background: Studies evaluating the economic burden of dermatological care in the transplant setting are currently not available in Australia., Aims: To evaluate the clinical and economic burden of benign and malignant skin lesions in renal transplant recipients in Central Queensland., Methods: A bottom-up approach was used to determine the clinical burden and direct costs from patient-level Medicare data obtained from Service Australia for skin lesions., Results: Seventy-six percent of the renal transplant population in Central Queensland participated in this study. The median age was 57.0 years (standard deviation ± 13.6) and the majority (61.8%) of participants were men. The mean duration after transplant surgery was 99.9 months (interquartile range, 73.2-126.6 months). During a 2-year follow-up, 22 (40%) patients were diagnosed with benign skin lesions, 21 (38%) with nonmelanoma skin carcinoma (NMSC) and one (2%) with melanoma. There was a total of 231 visits to clinicians for diagnostic and therapeutic skin procedures and the direct costs to Medicare was $48 806 Australian Dollars (AUD) or $30 427 US Dollars (USD). Approximately 86% of the total direct costs was spent for nonNMSC and mean direct costs for NMSC was $763 AUD (or $476 USD)., Conclusion: This Medicare data-based study provides further insight into the burgeoning clinical and economic burden of the care for benign and malignant skin lesions in the renal transplantation setting in Australia., (© 2023 The Authors. Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians.)

Background: Perineural invasion (PNI) in oral squamous cell carcinoma (OSCC) does not contribute to the current American Joint Committee on Cancer 8th edition (AJCC8) staging manual. This study seeks to validate the effect of multifocal PNI in a large cohort of patients., Methods: Patients undergoing primary surgical treatment of OSCC with curative intent between 1995 and 2022 was retrieved from two Australian head and neck databases. PNI was categorized as a single focus or multiple foci. Study end points included disease-specific survival (DSS) and overall survival (OS)., Results: Complete data for survival analysis was available in 993 patients. Multifocal PNI was associated with a 61% increased risk of death due to OSCC (HR 1.61, 95% CI 1.11-2.33, p = 0.014) and a 32% increased risk of death from any cause (HR 1.32, 95% CI 1.01-1.73, p = 0.045)., Conclusions: Multifocal PNI is a significant predictor of survival in OSCC., (© 2023 Wiley Periodicals LLC.)

Background/objective: A history of keratinocyte carcinoma (KC) is a risk factor for further KCs, but population-based studies quantifying the risk are lacking in Australia. We aimed to describe the risk of subsequent KCs after first KCs in the Australian state of Tasmania., Methods: Tasmanian residents identified in the Tasmanian Cancer Registry with a first histologically confirmed basal cell carcinoma (BCC), squamous cell carcinoma (SCC) or synchronous BCC and SCC (within 3 months) between January 1985 and December 2013 were followed up for at least 5 years for the development of a subsequent KC. Cumulative risk, incidence rates and standardised incidence ratios (SIRs) were calculated., Results: Those first diagnosed with BCC-only, SCC-only or synchronous BCC and SCC had (i) 5-year cumulative risks of subsequent KCs of 32%, 29% and 51%, (ii) annualised 5-year incidence rates of 8100/100,000 person-years at risk (PYR), 7747/100,000 PYR and 16,634/100,000 PYR and (iii) SIRs of 10.6 (95% CI: 10.5-10.6), 12.5 (95% CI: 12.4-12.6) and 313.0 (95% CI: 305.2-321.1), respectively. Risk estimates increased substantially when multiple (two or more) lesions of any type were diagnosed synchronously., Conclusions: In the first Australian population-based study to describe the risk of subsequent KCs according to histological types, around one in three Tasmanians diagnosed with first KCs were diagnosed with subsequent KCs within 5 years. The risk of subsequent KCs was higher among those with a history of multiple synchronous lesions, especially if they included both BCC and SCC lesions., (© 2022 The Authors. Australasian Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Australasian College of Dermatologists.)

Although deep learning (DL) has demonstrated impressive diagnostic performance for a variety of computational pathology tasks, this performance often markedly deteriorates on whole slide images (WSI) generated at external test sites. This phenomenon is due in part to domain shift, wherein differences in test-site pre-analytical variables (e.g., slide scanner, staining procedure) result in WSI with notably different visual presentations compared to training data. To ameliorate pre-analytic variances, approaches such as CycleGAN can be used to calibrate visual properties of images between sites, with the intent of improving DL classifier generalizability. In this work, we present a new approach termed Multi-Site Cross-Organ Calibration based Deep Learning (MuSClD) that employs WSIs of an off-target organ for calibration created at the same site as the on-target organ, based off the assumption that cross-organ slides are subjected to a common set of pre-analytical sources of variance. We demonstrate that by using an off-target organ from the test site to calibrate training data, the domain shift between training and testing data can be mitigated. Importantly, this strategy uniquely guards against potential data leakage introduced during calibration, wherein information only available in the testing data is imparted on the training data. We evaluate MuSClD in the context of the automated diagnosis of non-melanoma skin cancer (NMSC). Specifically, we evaluated MuSClD for identifying and distinguishing (a) basal cell carcinoma (BCC), (b) in-situ squamous cell carcinomas (SCC-In Situ), and (c) invasive squamous cell carcinomas (SCC-Invasive), using an Australian (training, n = 85) and a Swiss (held-out testing, n = 352) cohort. Our experiments reveal that MuSCID reduces the Wasserstein distances between sites in terms of color, contrast, and brightness metrics, without imparting noticeable artifacts to training data. The NMSC-subtyping performance is statistically improved as a result of MuSCID in terms of one-vs. rest AUC: BCC (0.92 vs 0.87, p = 0.01), SCC-In Situ (0.87 vs 0.73, p = 0.15) and SCC-Invasive (0.92 vs 0.82, p = 1e-5). Compared to baseline NMSC-subtyping with no calibration, the internal validation results of MuSClD (BCC (0.98), SCC-In Situ (0.92), and SCC-Invasive (0.97)) suggest that while domain shift indeed degrades classification performance, our on-target calibration using off-target tissue can safely compensate for pre-analytical variabilities, while improving the robustness of the model., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Background: Accurate epidemiological and outcomes data regarding cutaneous squamous cell carcinoma (cSCC) extending to the temporal bone is lacking., Methods: Retrospective analysis of 167 Australian patients with primary and peri-temporal bone cSCC., Results: cSCC extending from secondary subsites (93.4%) was 14 times more frequent than primary temporal bone SCC (6.6%). For patients who underwent curative surgery ± post-operative radiotherapy (n = 146, 87.4%), 5-year disease-free survival, locoregional recurrence-free survival, disease-specific survival, and overall survival was 53.0%, 59.4%, 67.9%, and 44.7%, respectively. External ear and pre-auricular tumors, salvage surgery, tumor size (≥40 mm medial-lateral), nodal disease, and involved margins were negative predictors of survival in multivariable analysis., Conclusion: In regions of high sun exposure, cSCCs extending to the temporal bone are more common than primary cancers. Outcomes are improved with clear margins, justifying the need for radical resection. Further research regarding pre-auricular cancers is required given poorer associated survival outcomes., (© 2022 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Background: Sentinel lymph node biopsy (SLNB) has been pivotal for pathological assessment of nodal status in cutaneous melanoma (CM) and oral cavity squamous cell carcinoma (OCSCC) thus crucial for staging. An ideal agent for lymphatic mapping should have a standardized preparation, appropriate accumulation in first-echelon nodes and no side effects. Tilmanocept, a CD206-receptor targeted novel radiotracer fulfils these properties. This study investigated Tilmanocept for lymphoscintigraphy and intraoperative identification of sentinel lymph nodes (SLN) in CM and OCSCC., Methods: This prospective cross sectional study examined patients who presented to Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney. Patients had biopsy proven tumours with clinically and radiologically negative regional lymph nodes. Tilmanocept guided lymphoscintigraphy was followed by intraoperative SLNs identification via handheld gamma probe. Primary endpoints were detection and retrieval rate of SLNs while secondary endpoints included pathological status of SLNs., Results: Thirty-five patients were included (26 with CM and 9 with OCSCC) with the most common primary tumour site for CM on the extremities (33.3%). Lymphoscintigraphy with Tilmanocept identified at least 1 SLN (sensitivity 100%) in all patients. SLNs were retrieved in all of patients intraoperatively (100% retrieval rate) with positive nodes found in 20% of patients. Tilmanocept also demonstrated 100% tissue specificity, with lymph nodal tissue confirmed histologically, with no false positives., Conclusion: Tilmanocept is a reliable radiotracer for assessing the nodal status in patients with CM and OCSCC. Our group is the first to evaluate the use of Tilmanocept in the Australian setting, adding to the limited studies worldwide., (© 2022 The Authors. ANZ Journal of Surgery published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Surgeons.)

Background: Sonic Hedgehog (SHH) pathway dysregulation is implicated in basal cell carcinoma (BCC) development. To evaluate the possible wider role of SHH gene variants in skin carcinogenesis, we assessed associations of genes in the SHH pathway with lifetime development of any keratinocyte cancer (KC), and with developing either BCCs or squamous cell carcinomas (SCCs) exclusively, in a 25-year prospective, population-based study of 1,621 Australians., Methods: We genotyped 795 unrelated adults with available blood samples: 311 cases with any KC (186 developing BCCs-only, 55 SCCs-only, 70 BCCs and SCCs) and 484 controls. We compared allele frequencies of 158 independent SNPs across 43 SHH genes between cases and controls, and performed a gene-based analysis., Results: We found associations between SNP rs4848627 (GLI2) (related to DNA synthesis in keratinocytes) and development of any KC (OR = 1.53; 95% CI = 1.06-2.13, P < 0.01) and SCCs exclusively (OR = 2.12; 95%CI = 1.39-3.23, P < 0.01). SNP rs3217882 located in CCND2 was associated with exclusive BCC development (OR = 1.43, CI = 1.12-1.82, P < 0.01). The gene-based analysis suggested an association of PRKACG (protein kinase cAMP-activated catalytic subunit gamma) with any KC (P = 0.013)., Conclusion: We conclude that variants located in genes in the SHH pathway may are involved in SCC as well as BCC development., (© 2022. The Author(s).)

Background: This study aimed to examine patients with facial nerve (VII) perineural spread (PNS) from cutaneous squamous cell carcinoma of the head and neck., Methods: Retrospective analysis of patients managed by an Australian tertiary center between 2000 and 2019., Results: Seventy three patients were included. Most presented with recurrent disease (89.0%) and simultaneous trigeminal nerve (V) involvement (67.1%). Of the 55 patients (75.3%) who received curative intent treatment, 48 received surgery plus/minus post-operative radiotherapy. In these patients, 5-year disease-free survival, disease-specific survival, and overall survival was 50.7%, 68.7%, and 58.1%, respectively. Pathological nodal disease, involved margins, increasing VII zonal extent, and concurrent zone 2 V PNS significantly worsened outcomes., Conclusion: High rates of recurrent disease reflects the importance of adequate treatment of the primary. Surgery and post-operative radiotherapy remains the mainstay treatment. Outcomes are improved in early-stage disease and with clear surgical margins, reinforcing the need for prompt diagnosis and intervention., (© 2022 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Background/objectives: To describe the incidence of primary cutaneous squamous cell carcinoma in coastal NSW Australia., Methods: The design is a case-controlled study of reported cSCC from 2016 to 2019 within a defined region of coastal southern NSW. Participants include all reported pathological diagnoses of cSCC in patients greater than 20 years of age. The main outcome measures the incidence and relative risk of cSCC., Results: The age-adjusted incidence rate of primary cSCC was 856/10 5 /year. Men over 60 years of age had an age-adjusted incidence rate of 2875/10 6 /year. Histologically diagnosed invasive SCC samples were included using SNOMED clinical term codes. Keratoacanthomas and SCC in situ SNOWMED codes were not included. SCC in situ results was found within the sample analysis and was offset by including one SCC per annum per person., Conclusions: The rates of cSCC are far higher than previously reported and demand a reappraisal of our national management of this disease., (© 2022 The Authors. Australasian Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Australasian College of Dermatologists.)

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., (© 2021 Royal Australasian College of Surgeons.)

Background: The 8th edition American Joint Committee on Cancer staging manual (AJCC8) introduced a separate staging system for head and neck cutaneous squamous cell carcinoma (HNcSCC) which parallels mucosal SCC and incorporates extranodal extension (ENE). This study aims to evaluate its prognostic utility., Methods: Univariate analysis of 1146 patients with metastatic HNcSCC from four Australian cancer centers was performed according to both AJCC 7th (AJCC7) and the 8th editions., Results: AJCC8 increased classification of 924 (80.6%) patients to either pN2a or pN3b and 341 patients (29.8%) from stage III to IV compared to AJCC7. The disease-specific survival (DSS) was not significantly different between pN1, pN2 or pN3a categories per AJCC8. Estimates of model performance for the AJCC8 pN staging revealed modest predictive capacity (Harrell's C of 0.62 for DSS)., Conclusions: The risk stratification according to pN classification of AJCC8 staging system performed poorly as a prognostic indicator., (© 2020 Wiley Periodicals LLC.)

Background/objectives: Therapeutic approaches to keratinocyte carcinoma rely on the accuracy of the biopsy to correctly identify, grade or subtype the tumour. Several studies have investigated the frequency and nature of histopathological discordance between the biopsy and final excision specimen. We analysed information extracted from an Australian Mohs micrographic surgery (MMS) database and compared similar studies., Methods: An Australian MMS database was retrospectively reviewed for a period of one year. Correlation was made between the preoperative lesion diagnosis based on the formal pathology report and the histopathological results reported at the time of MMS. A systematic PubMed review of similar articles was also performed., Results: A total of 464 cancers (406 BCC and 58 SCC) in 399 patients were included. The overall discrepancy rate in the histopathological classification of keratinocyte carcinoma in our study (42.2%) and the proportion of cases in which the biopsy underestimated the aggressiveness of the tumour (12.9%) were consistent with those found in similar studies. The percentage of biopsies that failed to identify an aggressive BCC subtype (31.6%), and that of biopsy-proven superficial BCC that demonstrated an invasive component in MMS (79.3%), were higher in our study than in comparable studies. The high prevalence of mixed histopathological subtypes, especially amongst BCC with discordant histopathological results, appeared as an important contributing factor., Conclusions: Despite subtle differences, the results from this Australian study support the results from similar studies and highlight that the biopsy report should be carefully interpreted in combination with the clinical findings., (© 2020 The Australasian College of Dermatologists.)

Objective: Oral squamous cell carcinoma (SCC) has been traditionally described as a highly lethal disease. This study aims to provide updated multi-institutional data on the survival of patients with oral SCC in Australia., Study Design: Retrospective survival analysis was performed between 2008 and 2016. All new patients with oral SCC treated with curative intent were recruited from 2 high-volume Australian head and neck oncology centers. Outcomes were measured in overall survival (OS), disease-specific survival (DSS), disease-free survival, and salvage rates for recurrences., Results: Survival analysis included 771 patients with oral SCC. Five-year OS and DSS were 66.1% and 79.7%, respectively. Stage I and II oral SCC had significantly better survival than higher stages. Five-year OS and DSS for patients with stage I SCC were 79.7% and 93.4%, respectively, and for patients with stage IVB they were 37.9% and 54.3%, respectively. Two hundred forty-nine patients had disease recurrence (32.3%), with 66 patients (26.5% remaining disease free post salvage treatment., Conclusion: Survival outcomes for oral SCC among Australian patients have improved, possibly due to advances in multidisciplinary care. Early detection of oral SCC leads to highly favorable prognosis; there is therefore an opportunity for routine oral cancer screening to be performed by community health practitioners with the aim of improving survival from oral SCC., (Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.)

Objective: Most guidelines advise no adjuvant radiotherapy in vulvar squamous cell carcinoma and a single occult intracapsular lymph node metastasis. However, several recent studies have questioned the validity of this recommendation. The aim of this study was to analyze the groin recurrence rate in patients with a single intracapsular positive lymph node treated without adjuvant radiotherapy., Methods: Patients with a single clinically occult intracapsular lymph node metastasis, treated without adjuvant radiotherapy, formed the basis for this study. Groin recurrences, and the risk of death, were analyzed in relation to the size of the metastasis in the lymph node and the lymph node ratio. Data were analyzed using SPSS, version 26.0 for Windows., Results: After a median follow-up of 64 months, one of 96 patients (1%) was diagnosed with an isolated groin recurrence and another two (2.1%) were diagnosed with a combination of a local and a groin recurrence. The only isolated groin recurrence occurred in a contralateral lymph node negative groin. Size of the metastasis and lymph node ratio had no impact on the groin recurrence risk, nor on survival. The 5-year actuarial disease-specific and overall survivals were 79% and 62.5% respectively. The 5-year actuarial groin recurrence-free survival was 97%., Conclusion: Because of the low risk of groin recurrence and the excellent groin recurrence-free survival, we recommend that adjuvant radiotherapy to the groin in patients with vulvar squamous cell carcinoma and a single occult intracapsular lymph node metastasis can be safely omitted to prevent unnecessary toxicity and morbidity., Competing Interests: Declaration of Competing Interest Authors do not declare any conflict of interest related to this paper., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: As the availability of Mohs micrographic surgery (MMS) continues to expand in Australia and incidence of keratinocyte cancer increases in adolescents and young adults, there has been rising interest in the use of MMS in this population., Objective: This study aimed to evaluate the characteristics of MMS cases in patients younger than 40 years., Methods: A review was performed of all MMS cases in patients younger than 40 years at the time of their surgery from 2012 to 2017 at the Skin and Cancer Foundation Australia, with comparison to a control group, aged older than 40 years. Patient, tumor and management characteristics were analyzed., Results: Four hundred ninety-three cases were eligible. Study and control groups differed significantly regarding gender (p < .001), tumor pathology (p < .001), anatomic site of tumor (p < .001), Mohs surgery stages (p = .039), defect size (p < .001), and repair method (p < .001)., Limitations: Retrospective study at a single institution., Conclusion: Mohs micrographic surgery cases in patients younger than 40 years exhibit unique patient and tumor characteristics influencing choice of repair method.

Background: The 8th edition American Joint Committee on Cancer nodal (N) staging of cutaneous squamous cell carcinoma of the head and neck (cSCCHN) is largely based on lymph node metastasis size, despite conflicting data in the literature. This study aimed to investigate the prognostic significance of largest node size in cSCCHN., Methods: Retrospective analysis of 94 patients undergoing curative-intent treatment for nodal cSCCHN with surgery ± radiotherapy at Liverpool Hospital, Sydney, Australia was conducted. Survival outcomes were assessed using multivariate Cox regression. The primary end point was disease-free survival (DFS). Objective measures of model performance were used in exploratory analyses to identify optimal size thresholds for predicting survival., Results: Nodal metastasis size significantly predicted DFS on multivariate analysis (hazard ratio 1.24; 95% confidence interval 1.06-1.46; P = 0.008). This prognostic impact occurred predominantly in parotid metastases (hazard ratio 1.27; 95% confidence interval 1.07-1.51; P = 0.006); each 1 cm increase in size increased the risk of recurrence or death by 27%, irrespective of the number of involved nodes. In parotid metastases, size thresholds of ≤3, 3-4.5 and >4.5 cm optimized prognostic discrimination. Extranodal extension (ENE) was associated with decreased DFS in nodes ≤3 cm in size (P = 0.025), but not in those >3 cm (P = 0.744)., Conclusion: Size is an important prognostic factor in cSCCHN with parotid metastases, with optimal thresholds of ≤3, >3-4.5 and >4.5 cm. The prognostic impact of ENE was seen only in nodal metastases ≤3 cm in size. These results may have important implications for node size thresholds and inclusion of ENE in the American Joint Committee on Cancer N staging categories., (© 2020 Royal Australasian College of Surgeons.)

Recent European and US studies reported increased risks of skin cancers associated with hydrochlorothiazide (HCTZ) treatment. Our study aimed to determine the risk of lip cancer and malignant melanoma among Australians prescribed HCTZ. We conducted a case-control study nested within a population of veterans residing in New South Wales in 2004-2015, using Australian Department of Veterans' Affairs data linked with cancer registrations, hospitalisation and prescription dispensings. Among DVA healthcare card holders 65 years and older, we identified incident cases of squamous cell carcinoma of the lip and of cutaneous melanoma, each matched with up to 20 controls through risk-set sampling. We estimated odds ratios (ORs) associating HCTZ use with each cancer using conditional logistic regression, adjusting for predefined confounders. For lip cancer (45 cases), ever-use of HCTZ yielded an OR of 2.6 (95% CI: 1.4-5.0) and high HCTZ use (≥25 000 mg) an OR of 4.7 (95% CI: 1.6-13.7). For cutaneous melanoma (659 cases), ever-use of HCTZ resulted in an OR of 1.2 (95% CI 1.0-1.5) and high HCTZ use in an OR of 1.2 (95% CI: 0.8-1.8). Our findings align with risk estimates from previous studies and provide further evidence that HCTZ's photosensitising properties may promote carcinogenesis in sun-exposed tissues., (© 2020 Commonwealth of Australia. © 2020 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Objectives: This study aimed to describe the longitudinal thromboembolism (TE) risk relative to the natural history of disease and clinical course of ROS1 rearranged non-small cell lung cancer (NSCLC)., Materials and Methods: Cases of ROS1-rearranged NSCLC from six Australian hospitals were pooled and evaluated for incidence, timing, predictors and outcomes of venous or arterial TE, as well as objective response rate (ORR) to active therapy and overall survival (OS)., Results: Of 42 patients recruited, 20 (48%) experienced TE; one (2%) arterial, 13 (31%) a pulmonary emboli (PE), and 12 (29%) a deep vein thrombosis. Among those with TE, six (30%) experienced multiple events, three as concurrent and three as recurrent diagnoses. The cumulative incidence of TE over time, adjusted for death as a competing risk factor, approached 50%. TE occurred prior to, during and post the peri-diagnostic period and occurred irrespective of treatment strategy. A thrombophilia was identified in n = 3/10 (30%) cases screened: in two factor V Leiden and in one anti-thrombin III (ATIII) deficiency. Median OS was 21.3 months in those with TE vs. 28.8 months in those without; hazard ratio 1.16 (95%CI 0.43-3.15). Respective ORR to first-line therapy with TE was 50% vs. 44% without TE in the chemotherapy arm and 67% vs. 50% in the targeted therapy arm., Conclusion: In the rare cancer subtype, ROS1, these real-world data demonstrate sustained TE risk beyond the diagnostic period irrespective of therapeutic strategy. High incidence of PE, concurrent TE, and recurrent TE warrant validation in larger cohorts. Consideration of primary thromboprophylaxis in ROS1 populations is recommended., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest directly related to this work however acknowledge the following associations outside the submitted work. Dr. Alexander has nothing to disclose. Dr. Pavlakis reports personal fees from Boerhinger Ingelheim, personal fees from Takeda, personal fees from Astra Zeneca, personal fees from BMS, personal fees from MSD, personal fees and other from Roche, grants and personal fees from Pfizer, personal fees from Novartis, personal fees from Amgen, personal fees from Merck KgA, personal fees from Merck Serono, grants from Bayer, personal fees from Ipsen, outside the submitted work. Dr. John reports personal fees from Ignyta, personal fees from Roche, personal fees from AstraZeneca, personal fees from Novartis, personal fees from Pfizer, personal fees from Merck, personal fees from BMS, outside the submitted work. Dr. O’Connell has nothing to disclose; Dr. Kao reports personal fees from Pfizer, personal fees from Novartis, personal fees from Roche, during the conduct of the study; personal fees from Boehringer, personal fees from BMS, personal fees from MSD, grants and personal fees from Astra Zeneca, outside the submitted work. Dr. Hughes reports personal fees from Pfizer, personal fees from Roche, personal fees from Merck Sharpe and Dohme, personal fees from Bristol Meyers Squibb, personal fees from AstraZeneca, grants from Amgen, outside the submitted work. Dr. Lee reports personal fees from Munipharma, outside the submitted work; Dr. Hayes has nothing to disclose. Dr. Howell has nothing to disclose. Dr. Clarke has nothing to disclose. Dr. Millward reports personal fees from Pfizer, during the conduct of the study; personal fees from Astra-Zeneca, personal fees from Bristol Myers Squibb, personal fees from Roche, personal fees from Merck Sharp & Dohme, outside the submitted work. Dr. Burbury has nothing to disclose. Dr. Solomon reports personal fees from Pfizer, personal fees from Roche/Genetech, personal fees from Novartis, personal fees from Merck, personal fees from Bristol Myers Squibb, personal fees from AstraZeneca, personal fees from Loxo Oncology, outside the submitted work. Dr. Itchins reports personal fees from Pfizer, personal fees from Roche, outside the submitted work., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The availability of Mohs micrographic surgery (MMS) in Australia has increased dramatically since its inception in the 1980s., Objective: This study aimed to describe the evolution of MMS practices at the Skin and Cancer Foundation Australia (SCFA) over the past 20 years (1997-2017)., Methods: Retrospective analysis of Mohs surgery cases at SCFA in 2017, 2007, and 1997, comparing data on sex, age, tumor type and site, initial tumor and final defect size, number of surgical stages and sections, and closure management. The present study is limited by being a retrospective analysis from a single institution., Results: There was a 415% increase in the number of Mohs surgery cases from 1997 to 2017, and a significant increase in Mohs surgery-treated squamous cell carcinoma. The preoperative tumor and final defect size have decreased. More side-to-side closures and fewer grafts are being performed over time., Limitations: Retrospective analysis from a single institution., Conclusion: Over the last 20 years, MMS has remained appropriate in its application and is being increasingly used for treatment of squamous cell carcinoma suggesting improved access.

Background: Cemiplimab has shown substantial antitumour activity in patients with metastatic cutaneous squamous cell carcinoma. Patients with locally advanced cutaneous squamous cell carcinoma have poor prognosis with conventional systemic therapy. We present a primary analysis of the safety and antitumour activity of cemiplimab in patients with locally advanced cutaneous squamous cell carcinoma., Methods: This pivotal open-label, phase 2, single-arm trial was done across 25 outpatient clinics, primarily at academic medical centres, in Australia, Germany, and the USA. Eligible patients (aged ≥18 years with histologically confirmed locally advanced cutaneous squamous cell carcinoma and an Eastern Cooperative Oncology Group performance status of 0-1) received cemiplimab 3 mg/kg intravenously over 30 min every 2 weeks for up to 96 weeks. Tumour measurements were done every 8 weeks. The primary endpoint was objective response, defined as the proportion of patients with complete or partial response, according to independent central review as per Response Evaluation Criteria in Solid Tumors version 1.1 for radiological scans and WHO criteria for medical photography. Data cutoff was Oct 10, 2018, when the fully enrolled cohort reached the prespecified timepoint for the primary analysis. Analyses were done as per the intention-to-treat principle. The safety analysis comprised all patients who received at least one dose of cemiplimab. This study is registered with ClinicalTrials.gov, number NCT02760498., Findings: Between June 14, 2016, and April 25, 2018, 78 patients were enrolled and treated with cemiplimab. The median duration of study follow-up was 9·3 months (IQR 5·1-15·7) at the time of data cutoff. An objective response was observed in 34 (44%; 95% CI 32-55) of 78 patients. The best overall response was ten (13%) patients with a complete response and 24 (31%) with a partial response. Grade 3-4 treatment-emergent adverse events occurred in 34 (44%) of 78 patients; the most common were hypertension in six (8%) patients and pneumonia in four (5%). Serious treatment-emergent adverse events occurred in 23 (29%) of 78 patients. One treatment-related death was reported that occurred after onset of aspiration pneumonia., Interpretation: Cemiplimab showed antitumour activity and an acceptable safety profile in patients with locally advanced cutaneous squamous cell carcinoma for whom there was no widely accepted standard of care., Funding: Regeneron Pharmaceuticals and Sanofi., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The incidence of skin cancers in Australia continues to rise. Early detection and timely management are required., Objective: This article presents a framework for skin examinations in primary care and outlines the various measures available to facilitate early skin cancer detection. Common characteristics of malignant cancers are also discussed., Discussion: Skin cancer awareness campaigns encourage patients to see their general practitioners (GPs) for complete skin examination. GPs are expected to correctly identify benign and malignant skin lesions and understand their high risk patients. A systematic approach to the skin examination combined with knowledge and awareness of diagnostic tools can aid in the early detection of skin malignancies, and prompt escalation as necessary.

Background: To investigate the prognostic significance of positron emission tomography (PET) parameters from F-18 fluorodeoxyglucose (FDG) PET scans performed pre- and post- chemo-radiotherapy (CRT) for squamous cell carcinoma of the anal canal (AC)., Methods: From January 2013 to January 2017, 19 patients with non-metastatic AC enrolled on a prospective trial underwent FDG-PET/CT imaging before and 12 weeks following CRT. A computer-generated volume of interest (VOI) was snapped around the primary tumour using six different standard uptake value (SUV) thresholds and the following parameters were extracted: SUV max, mean, median, standard deviation and peak as well as metabolic tumour volume (MTV) and total lesion glycolysis. Exact logistic regression and ROC AUC analyses were performed for each metric at each timepoint., Results: With a median follow up of 15.8 months, 3/19 patients had a local recurrence and 5/19 had any recurrence. On post-CRT PET, the median SUV within a VOI bounded by an SUV of 3 correlated with local recurrence (p < 0.01) and demonstrated excellent discrimination (ROC AUC 1.00, perfect separation was achieved at a median SUV of 3.38). The mean SUV at this threshold did not quite reach significance for prediction of local recurrence (p = 0.06) but demonstrated excellent discrimination (ROC AUC 0.91). The MTV bounded by a threshold of 41% SUVmax on the pre-CRT PET predicted for any recurrence (p = 0.03) and showed excellent discrimination (ROC AUC 0.89)., Conclusions: FDG-PET parameters are predictive of recurrence in AC. FDG-PET may represent a valuable tool for prognostication and response assessment in AC., Trial Registration: ANZCTR, ACTRN12614001219673 . Registered 19 November 2014 - Retrospectively registered.

Importance: There is limited research examining the incidence of nonmelanoma skin cancer (NMSC) in heart and lung transplant recipients in Australia., Objective: To determine the frequency of and risk factors for NMSC in a cohort of Australian heart and lung transplant recipients., Design, Setting, and Participants: A retrospective cohort study was conducted at an Australian tertiary center where heart and lung transplants are performed between March 21 and December 14, 2016. A consecutive sample of 94 patients who underwent heart and/or lung transplant presenting for outpatient dermatologic review were evaluated. Data analysis was conducted between April 18 and October 30, 2017., Exposures: Risk factors examined for association with posttransplantation NMSC included age at the time of transplantation, sex, skin phenotype, UV radiation exposure, history of allograft rejection, history of smoking, history of skin cancer prior to transplant, and transplant type., Main Outcomes and Measures: The primary outcome measure was the occurrence of posttransplantation NMSC. The probabilities of developing NMSC in general, and squamous cell carcinoma and basal cell carcinoma specifically, were separately summarized based on Kaplan-Meier analysis. Association of risk factors with development of NMSC was examined using univariable and multivariable Cox proportional hazards regression analysis., Results: Of the 94 study participants, 58 (62%) were men; median age at transplantation was 51.9 years (range, 15.1-69.7 years). There were 801 posttransplantation skin cancers in 57 (61%) of the patients who underwent heart and/or lung transplant. The probabilities for NMSC were 41% (95% CI, 31%-53%) at 5 years and 67% (95% CI, 55%-78%) at 10 years; for basal cell carcinoma, 27% (95% CI, 18%-38%) at 5 years and 53% (95% CI, 40%-67%) at 10 years; and for squamous cell carcinoma, 33% (95% CI, 24%-45%) at 5 years and 62% (95% CI, 50%-74%) at 10 years. On multivariable analysis, older age at transplantation was associated with the development of NMSC (hazard ratio [HR], 1.07/1 year; 95% CI, 1.04-1.10; P < .001) and history of pretransplant skin cancer was associated with development of basal cell carcinoma (HR, 4.56; 95% CI, 1.67-12.42; P = .003). A Fitzpatrick skin type III to VI was associated with a decreased risk of NMSC (HR, 0.42; 95% CI, 0.24-0.74; P = .003). Sex, transplanted organ, UV radiation exposure, and history of allograft rejection were not associated with an increased risk of skin cancer., Conclusions and Relevance: In this study of Australian heart and lung transplant recipients, there was a probable high frequency of NMSC. Routine dermatologic surveillance at frequent intervals is advised for similar populations.

Background: The American Joint Committee on Cancer (AJCC) has changed the staging system of oral squamous cell carcinoma (OSCC) in the 8th edition of its staging manual to include depth of invasion (DOI) of the primary tumor as a modifier to the T category and extranodal extension (ENE) to upstage node positive OSCC. This study aims to evaluate the performance of the AJCC 8 pathologic staging system in OSCC and compare it to its predecessor (AJCC 7)., Methods: Analysis of 663 patients with OSCC from a prospective database was performed using the Cox proportional hazards competing risk model. The prognostic performance of the pathologic staging system was assessed using the Akaike Information Criterion (AIC) and Harrell's concordance index (C-index)., Results: AJCC 8 led to upstaging of 35.6% (N = 235) of patients in this cohort. Both AJCC 7 and 8 show limited monotonicity and poor stratification between stage groups I to III. The estimates for model performance reveal that AJCC 8 has modest predictive capacity for overall survival (OS) and disease specific survival (DSS) (Harrell's C of 0.70 and 0.74, respectively) but is superior to AJCC 7 (Harrell's C of 0.65 and 0.69, respectively)., Conclusions: The AJCC 8 staging system is more complex than its former version due to the inclusion of DOI and ENE. Compared with AJCC 7, it performs better in stratifying survival of OSCC patients by stage., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Anal squamous cell carcinoma (SCC) is a rare malignancy. The purpose of this study was to review a single institution's experience., Methods: All patients with anal SCC from St John of God Subiaco Hospital database were identified over a 10-year period (2006-2016). Patients with stage 1 anal verge tumours underwent wide local excision, all remaining patients were offered chemoradiation (CRT) as an initial treatment modality (a fluorouracil-based regimen in conjunction with mitomycin). Outcomes included recurrence, overall survival and survival following salvage surgery., Results: Forty-seven patients were identified. Median age was 60 years and median follow-up was 2.73 years. Five-year rates of recurrence and overall survival were 35.8% (95% confidence interval (CI) 23.2-52.4%) and 65.4% (95% CI 47.0-78.7%), respectively. Locoregional failure occurred most commonly at the primary site. Eight patients underwent salvage abdominoperineal resection for persistent or recurrent disease, and four of these patients died within 5 years., Conclusion: CRT is a proven and reasonable effective approach in managing anal cancer. Observed recurrence and overall survival rates in this study resemble the published data. Despite newer methods of treatment being investigated, the treatment for anal SCC has not significantly changed in the past four decades and novel approaches are needed to further improve outcomes., (© 2018 Royal Australasian College of Surgeons.)

Background: The goals of this multinational retrospective study were to describe treatment patterns and survival outcomes by receipt of molecular testing and molecular status of patients with advanced non-small cell lung cancer (NSCLC)., Methods: This chart review study, conducted in Italy, Spain, Germany, Australia, Japan, Korea, Taiwan, and Brazil, included 1440 patients with newly diagnosed advanced (stage IIIB/IV) NSCLC initiating systemic therapy from January 2011 through June 2013, with follow-up until July 2016. We evaluated treatment patterns and survival by histology, line of therapy, molecular testing, and test results for epidermal growth factor receptor (EGFR) mutation and/or anaplastic lymphoma kinase (ALK) rearrangement. Country-specific data were analyzed descriptively and presented as ranges (lowest to highest country). Overall survival (OS) was estimated using Kaplan-Meier method., Results: Patients with ≥1 molecular test varied from 43% (Brazil) to 85% (Taiwan). Numerically greater proportions of patients who were female, Asian, or never/former-smokers, and those with nonsquamous histology or stage-IV NSCLC, received a test. Testing was common for nonsquamous NSCLC (54%, Brazil, to 91%, Taiwan), with positive EGFR and ALK tests from 17% (Brazil and Spain) to 67% (Taiwan) and from 0% (Brazil) to 60% (Taiwan), respectively. First-line treatment regimens for nonsquamous NSCLC with positive EGFR/ALK tests included targeted therapy for 30% (Germany) to 89% (Japan); with negative/inconclusive test results, platinum-based combinations for 88% (Japan) to 98% (Brazil); and if not tested, platinum-based combinations for 80% (Australia) to 95% (Japan), except in Taiwan, where 44% received single agents. Median OS from first-line therapy initiation was 10.0 (Japan) to 26.7 (Taiwan) months for those tested and 7.6 (Australia/Brazil) to 19.3 (Taiwan) months for those not tested., Conclusions: We observed substantial variation among countries in testing percentages, treatment patterns, and survival outcomes. Efforts to optimize molecular testing rates should be implemented in the context of each country's health care scenario., Competing Interests: Dae Ho Lee reports honoraria from AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, CJ Healthcare, Eli Lilly, Jansen, Merck, MSD, Mundipharma, Novartis, Ono, Pfizer, Roche, and Samyang Biopharm for participating in advisory boards; and receipt of consulting fees from the Ministry of Food and Drug Safety (MFDS), Korea, and Health Insurance Review and Assessment Service (HIRA), Korea. Ming-Sound Tsao reports honoraria for advisory board meetings from AstraZeneca, Bristol-Myers Squibb, Pfizer, Ventana/Roche, and Merck. Hiroshi Isobe has received payment for speaking engagements from AstraZeneca, Bristol-Myers Squibb, Kyowa Hakko Kirin, Chugai, Boehringer Ingelheim, Ono Pharmaceutical Co. Ltd., and Eli Lilly Japan, K.K. Smita Kothari, Ashwini Arunachalam, Xiting Cao, and Thomas Burke are employees of Merck & Co., Inc., Kenilworth, NJ, USA, which supplied the funding for this study. Amparo Valladares is an employee of Merck Sharp & Dohme de España S.A., Madrid, Spain. All other authors declare that they have no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Many plastic surgery departments in Australasia have experienced increasing referrals for management of skin lesions. This has driven a demand for new strategies to decrease patient waiting time and administrative costs. The aim of this study was to determine if a purpose-built See and Treat skin cancer clinic could provide a faster skin cancer treatment pathway with comparable clinical outcomes and acceptability to patients., Methods: This was a prospective observational study of patients treated through the See and Treat clinic with a retrospective control cohort. The prospective 'See and Treat' cohort included a consecutive series of 106 patients, while the retrospective cohort included a consecutive series of 200 patients. Patient demographics, time from referral to surgery and operative measures were analysed. One hundred patients in the prospective cohort completed an anonymous satisfaction survey regarding their treatment., Results: The average time from referral to surgery was reduced from 121 days in the retrospective cohort to 60 days in the See and Treat cohort (P < 0.001). Rates of complete excision of malignant and premalignant lesions were not different between the two groups, being 93% (178/191) and 91% (76/84), respectively (P = 0.609). Ninety-five percent (95/100) of patients were satisfied with their See and Treat experience overall., Conclusion: We show that a considerable reduction in the time between referral and surgery can be achieved through a See and Treat clinic without compromise of the success of surgical treatment. Moreover, such a treatment pathway has been shown to be acceptable, and largely preferable, to patients., (© 2017 Royal Australasian College of Surgeons.)

Background: The incidence of oropharyngeal squamous cell carcinoma in the Western world is increasing, with the human papillomavirus epidemic implicated in this observed trend. The optimal treatment modality is yet undetermined regarding oncological outcomes., Methods: This study comprised 98 patients with oropharyngeal squamous cell carcinoma, treated with either primary transoral surgery with adjuvant therapy or primary chemoradiotherapy with curative intent, between 2008 and 2012. Clinicopathological characteristics including tumour-node-metastasis stage, human papillomavirus status, treatment modality, recurrence and overall survival were collated., Results: Five per cent of primary surgical patients had locoregional recurrences compared with 25 per cent of primary chemoradiotherapy patients. A lower rate of locoregional recurrence was observed in the human papillomavirus positive group., Conclusion: This paper reports higher rates of overall survival and local control for oropharyngeal squamous cell carcinoma treated with primary surgery compared with primary chemoradiotherapy. This reflects overall lower tumour stage and higher human papillomavirus status in this group.

Background: Longitudinal studies of histological outcomes after anal cytological screening in men who have sex with men (MSM) are rare. This study measured the positive predictive values (PPVs) of each level of baseline cytological abnormality in MSM in Sydney, Australia, over a 12-month period., Methods: The Study of the Prevention of Anal Cancer is a 3-year prospective study of the natural history of anal human papillomavirus infection in MSM at least 35 years old. For each participant with a baseline cytological abnormality, the worst histology was recorded at the baseline high-resolution anoscopy and at 6 and 12 months. PPVs for a histological high-grade squamous intraepithelial lesion (HSIL) diagnosis were calculated for each level of baseline cytological abnormality at each time point., Results: Among 424 men who completed 3 visits, the PPV of a cytological HSIL increased from 71.6% at the baseline to 86.4% at 6 months and to 92.6% at 12 months (P < .001). For cytological atypical squamous cells, cannot rule out high-grade squamous intraepithelial lesion (ASC-H), the PPV increased from 51.5% at the baseline to 69.7% at 6 months and to 75.8% at 12 months (P = .004). At each time point, the PPV of a cytological HSIL was significantly higher than the PPV of ASC-H. The PPV of low-grade cytology reports was significantly lower than the PPV of ASC-H at each time point., Conclusions: In a cohort of MSM, a baseline histological HSIL diagnosis after an HSIL cytoprediction is high, and it increases with further examinations over the course of 12 months. Lower levels of cytological abnormalities have significantly lower PPVs. These data can inform patient management and the quality assessment of each aspect of the screening pathway. Cancer Cytopathol 2018;126:136-44. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Background: Weight loss remains significant in patients with head and neck cancer, despite prophylactic gastrostomy and intensive dietary counseling. The aim of this study was to improve outcomes utilising an early nutrition intervention., Methods: Patients with head and neck cancer at a tertiary hospital in Australia referred for prophylactic gastrostomy prior to curative intent treatment were eligible for this single centre randomised controlled trial. Exclusions included severe malnutrition or dysphagia. Patients were assigned following computer-generated randomisation sequence with allocation concealment to either intervention or standard care. The intervention group commenced supplementary tube feeding immediately following tube placement. Primary outcome measure was percentage weight loss at three months post treatment., Results: Recruitment completed June 2015 with 70 patients randomised to standard care (66 complete cases) and 61 to intervention (56 complete cases). Following intention-to-treat analysis, linear regression found no effect of the intervention on weight loss (10.9±6.6% standard care vs 10.8±5.6% intervention, P=0.930) and this remained non-significant on multivariable analysis (P=0.624). No other differences were found for quality of life or clinical outcomes. No serious adverse events were reported., Conclusions: The early intervention did not improve outcomes, but poor adherence to nutrition recommendations impacted on potential outcomes.

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., (© 2017 Wiley Periodicals, Inc.)

Introduction: Anal squamous cell carcinoma is preceded by persistent infection with high-risk human papillomavirus (HPV) and the cancer precursor, high-grade squamous intraepithelial lesion (HSIL). Detection of specific HPV genotypes and HPV-related biomarkers may be an option for primary anal screening. However, more data on the natural history of HPV-related anal lesions are required. The outcomes from this study will enhance our understanding of the clinical and biological behaviour of HPV-related anal lesions and inform the development of future HPV genotype and/or biomarker screening tests., Methods and Analysis: HIV-negative and HIV-positive men who have sex with men, aged 35 years and over, recruited from community-based settings in Sydney, Australia, attend 6 clinic visits over 3 years. At the first 5 visits, participants undergo a digital anorectal examination, an anal swab for HPV genotyping and anal cytology, and high-resolution anoscopy with directed biopsy of any visible abnormalities that are suggestive of any abnormality suspicious of SIL. Tissue sections from participants diagnosed with histologically confirmed HSIL at the baseline clinic visit will undergo laser capture microdissection, HPV detection and genotyping, and quantitation of CpG methylation in baseline and follow-up biopsies. Histological and cytological findings in combination with HPV genotyping data will be used to identify persistent HSIL. HSIL will be stratified as non-persistent and persistent based on their status at 12 months. The performance of HPV genotype and methylation status in predicting disease persistence at 12 months will be assessed, along with associations with HIV status and other covariates such as age., Ethics and Dissemination: The St Vincent's Hospital Ethics Committee granted ethics approval for the study. Written informed consent is obtained from all individuals before any study-specific procedures are performed. Findings from this study will be disseminated to participants and the community through study newsletters, and through peer-reviewed publications and international conferences., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Whether susceptible people develop both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) or one type exclusively during life is unknown. We investigated this in an Australian community cohort of 1,191 adults aged 25-75 years by recording all new BCCs and SCCs for 16 years in people with no previous keratinocyte cancer. Among those who developed multiple skin cancers, age- and sex-specific incidence rates per 100,000 were calculated for those who developed BCC exclusively, SCC exclusively, or BCC and SCC. Corresponding relative risks (and 95% confidence intervals) were estimated by Poisson regression. During follow-up, 116 people developed multiple keratinocyte cancers: 65 (56%) developed BCC exclusively (range 2-8 per person); 18 (16%) developed SCC exclusively (2-5 per person); and 28% developed both types. Of the 116, 88 had a BCC first, of whom 74% subsequently developed only BCCs, and 28 had SCC first, of whom 64% subsequently developed only SCCs. Incidence rates did not differ by sex in the BCC-only, SCC-only, or mixed groups, but they increased significantly with age especially in the SCC-only group. These findings suggest that the majority of people are prone to develop one type rather than a mix of keratinocyte cancers.

Background: In Australia, squamous cell carcinoma (SCC) of the lip is a consequence of chronic sun exposure and treated as a nonmelanoma skin cancer. Patients may be recommended radiotherapy (RT) as a treatment modality., Objective: To analyze the outcome of patients with early-stage SCC of the lip treated with definitive RT at Westmead Hospital, Sydney, Australia, between 1980 and 2012., Methods and Materials: Ninety-three patients with early-stage SCC of the lip underwent RT. All patients were clinically node negative based on examination and/or relevant investigations. Retrospective chart review was performed. Patients treated since 2000 had data collected and entered prospectively., Results: The most frequently involved site was the lower lip (93%). Fifty-six patients (60%) had T1N0 and 37 patients (40%) had T2N0 disease. Most patients were treated with superficial or orthovoltage RT, with the median RT dose delivered 55 Gy (range, 40 to 70 Gy). Local recurrence occurred in 5 patients (5%), whereas regional metastases developed in 5 patients (5%). One patient developed concurrent local and regional relapse. No patient developed distant metastases. The 5-year recurrence-free survival was 90%., Conclusion: The findings confirm the efficacy of RT as an efficacious treatment option in early-stage lip SCC.

This article by the Perineural Invasion (PNI) Registry Group aims to clarify clinical and histopathological ambiguities surrounding PNI in non-melanoma skin cancer (NMSC). PNI is reportedly present in approximately 2-6% of cases of NMSC and is associated with greater rates of morbidity and mortality. The distinction between clinical PNI and incidental PNI is somewhat unclear, especially in regard to management and prognosis. One important objective of the PNI Registry is to develop a standardised method of classifying perineural invasion. Hence, in this article we propose a definition for PNI and for its sub-classification. This article also provides a critical analysis of the current literature on the treatment of incidental PNI by evaluating the key cohort studies that have investigated the use of surgery or radiotherapy in the management of incidental PNI. At present, there are no universal clinical guidelines that specify the acceptable treatment of NMSC exhibiting incidental PNI. Consequently, patients often receive surgery with varying wider margins, or radiotherapy despite the limited evidence substantiating such management options. It is evident from the existing literature that current opinion is divided over the benefit of adjuvant radiotherapy. Certain prognostic factors have been proposed, such as the size and depth of tumour invasion, nerve diameter, the presence of multifocal PNI and the type of tumour. The PNI Registry is a web-based registry that has been developed to assist in attaining further data pertaining to incidental PNI in NMSC. It is envisaged that this information will provide the foundation for identifying and defining best practice in managing incidental PNI., (© 2013 The Australasian College of Dermatologists.)

Essential features of the epidemiology and photobiology of cutaneous malignant melanoma (CMM) in Norway were studied in comparison with data from countries at lower latitudes. Arguments for and against a relationship between ultraviolet radiation (UV) from sun and artificial light and CMM are discussed. Our data indicate that UV is a carcinogen for CMM and that intermittent exposures are notably melanomagenic. This hypothesis was supported both by latitude gradients, by time trends and by changing patterns of tumor density on different body localizations. However, even though UV radiation generates CMM, it may also have a protective action and/or an action that improves prognosis. There appears to be no, or even an inverse latitude gradient for CMM arising on non-UV exposed body localizations (uveal melanoma, CMMs arising in the vulva, perianal/anorectal regions, etc.). Furthermore, CMM prognosis was gradually improved over all years of increasing incidence (up to 1990), but during the past 20 years, incidence rates stabilized and prognosis was not improved significantly. Comparisons of skin cancer data from Norway, Australia and New Zealand indicate that squamous cell carcinoma and basal cell carcinoma are mainly related to annual solar UVB fluences, while UVA fluences play a larger role of CMM.

Anal squamous cell carcinoma is more common in HIV-positive homosexual men than in the general population and prognosis worsens with increasing tumour size. To identify opportunities for earlier diagnosis, we aimed to determine size and visibility of anal squamous cell carcinoma at diagnosis. We conducted a retrospective review of medical records between 1992 and 2010 from one hospital radiotherapy centre, a major centre for HIV care, in Melbourne, Australia. Of 128 cases of anal squamous cell carcinoma, 24 (19%) were in HIV-positive men. At diagnosis, half (52%) of the tumours were externally visible and mean estimated tumour size was 36 mm (29 mm in HIV-positive and 38 mm in HIV-negative patients; p = 0.04) and 114/121 (94%) tumours were 1 cm or larger. The most frequent symptoms were bleeding (43%) and pain (36%) and mean duration of symptoms was 22 weeks. This suggests most anal squamous cell carcinoma were visible or palpable for some time before diagnosis, meaning that screening high-risk groups by anal inspection and palpation is plausible.