Surgery (St Vincent's) - Research Publications

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    Knowledge and attitudes of Australian dermatologists towards sentinel lymph node biopsy for melanoma: a mixed methods study.
    Smith, AL ; Watts, CG ; Robinson, S ; Schmid, H ; Goumas, C ; Mar, VJ ; Thompson, JF ; Rapport, F ; Australian Melanoma Centre of Research Excellence Study Group, ; Cust, AE (Wiley, 2021-05)
    BACKGROUND/OBJECTIVES: In melanoma management, sentinel lymph node biopsy (SLNB) is used to stage patients and to indicate prognosis. More recently, it has been used to select patients for adjuvant therapy. This study aimed to report knowledge of and attitudes towards SLNB for patients with melanoma among Australian dermatologists. METHODS: Mixed methods study using cross-sectional questionnaires (n = 88) and semi-structured interviews (n = 13), May-September 2019. RESULTS: Of the dermatologists surveyed, 56% thought SLNB had an important role in melanoma management, 26% were unsure and 18% thought SLNB unimportant. Of the 92% who would discuss SLNB with their patients, the main stated value of SLNB was for assessing eligibility for adjuvant therapies (79%); only 60% indicated SLNB was of value for providing prognostic information, and just over half (53%) thought it could improve staging. Interview data indicated that attitudes towards SLNB are shifting among dermatologists, driven by data from landmark clinical trials and the influence of professional networks. Accordingly, interviewees adopted one of three positions in relation to SLNB: (a) believed in utility of SLNB and adhered to the guidelines; (b) were unconvinced about utility of SLNB but adhered to the guidelines; and (c) were unconvinced about utility of SLNB and did not adhere to the guidelines. CONCLUSION: Although most of the dermatologists surveyed were familiar with and follow the SLNB recommendations, some disagreement with and distrust of the recommendations was evident. Greater acceptance of the SLNB recommendations appeared to be driven by the improved outcomes demonstrated in stage III patients receiving adjuvant systemic therapy.
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    Characterising the immune microenvironment in liposarcoma, its impact on prognosis and the impact of radiotherapy
    Snow, H ; Mitchell, C ; Hendry, S ; McKinley, M ; Byrne, D ; Ngan, S ; Chander, S ; Chu, J ; Desai, J ; Bae, S ; Henderson, M ; Choong, P ; Gyorki, D (WILEY, 2021-01)
    BACKGROUND AND OBJECTIVES: Limited literature exists examining the immune microenvironment in liposarcoma, particularly with regard to the impact of radiotherapy. A major problem is the lack of scoring system for the tumour-infiltrating lymphocytes (TILs) in sarcoma. This study aims to describe the immune environment pre- and postradiotherapy and identify the optimal immune infiltrate scoring system for sarcoma. METHODS: Thirty-nine paired tissue samples (pre- and postradiotherapy) from patients with liposarcoma were scored by two pathologists for TILs using pre-existing systems (for breast cancer and melanoma) and compared for interobserver reliability. Immunohistochemical staining was performed for various immune markers. RESULTS: The TIL scoring system for breast cancer yielded perfect agreement (κ = 1.000). 21% of patients had increased TILs after radiotherapy, 87.5% of whom had dedifferentiated liposarcoma. Immune suppressor expression was increased frequently after radiotherapy (CD68 increased in 59.4%, PD-L1 increased in 25%). Immune effector expression (CD8) was unchanged in 84.4%. CONCLUSIONS: Breast cancer TIL scoring is reproducible in liposarcoma and has high interobserver reliability. Radiotherapy was observed to have a limited impact on immune effectors but seemed to have more impact in upregulating immune suppressors, suggesting radiotherapy may contribute to disease control through immunomodulatory effects. Dedifferentiated liposarcoma represents a uniquely responsive subtype.
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    Radiation-associated breast cancers in a late-effects cohort: Long-term surveillance is essential
    Koo, E ; Henderson, MA ; Dwyer, M ; Skandarajah, AR (WILEY, 2020-12)
    Aims Survivors of childhood, adolescent, and young adulthood malignancies have an increased risk of subsequent primary malignancies, particularly after exposure to therapeutic radiation. This study aims to evaluate the mode of surveillance and surveillance compliance, incidence and mode of detection of breast cancer, breast cancer phenotype, and outcomes after radiation‐associated breast cancer (RBC) in a late‐effects cohort. Methods Women exposed to therapeutic radiation attending the late effects service from 1st January 2000 to 20th February 2013. All invasive and in‐situ cancers, benign tumors, and deaths were evaluated. The incidence of breast cancer was compared to the Australian general population. Compliance with breast surveillance recommendations, clinicopathological features, and management of breast cancers were examined. Results The prevalence of RBC was 17.1%. Twenty‐eight cases of RBC occurred in 24 women, out of 140 women exposed to chest radiation. Patients whose first attendance was ≥15 years after radiation exposure experienced the highest incidence of RBC at 23%. The incidence of breast cancer was 11.2 times the general population (P < .001). Compliance with surveillance mammography was observed in 18.4%. Breast cancers diagnosed after the first attendance to the service were more likely screen‐detected (P = .002). Most were hormone receptor positive (84.0%), invasive ductal carcinomas (82.1%), and managed with mastectomy (89.3%). Conclusions Patients attending a dedicated late effects service have a high burden of subsequent malignancies generally occurring after long latency. Judicious management with adherence to long‐term surveillance guidelines is advocated.
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    Surgical management of recurrent cutaneous squamous cell carcinoma of the head and neck after definitive surgery and radiotherapy
    Toppi, J ; Tham, YS ; Webb, A ; Henderson, MA ; Rischin, D ; Magarey, MJR (WILEY, 2020-07)
    BACKGROUND: Surgery is the primary treatment for patients with recurrent head and neck cutaneous squamous cell carcinoma (cSCC) who have previously been treated by definitive surgery and radiotherapy. There are limited published data to direct management and the role of immunotherapy is currently under evaluation. METHODS: This was a retrospective study of patients with at least stage III recurrent head and neck cSCC previously managed by definitive surgery and radiotherapy. RESULTS: A total of 30 patients met the inclusion criteria. Eighty-seven percent were male and the median age at the time of surgery was 79 years. After salvage surgery, 7% developed local recurrence and 43% regional or distant failure. The 2-year overall survival and disease-free survival were 45% (95% confidence interval 24-64) and 11% (95% confidence interval 1-34), respectively. Advanced age was associated with a higher risk of overall mortality (P < 0.05). CONCLUSION: Patients with recurrent head and neck cSCC in the setting of previous radiotherapy have high recurrence rates with poor survival justifying consideration for treatment with anti-PD-1 immunotherapy strategies.
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    Cutaneous leiomyosarcoma: dermal and subcutaneous
    Wong, GN ; Webb, A ; Gyorki, D ; McCormack, C ; Tran, P ; Ngan, SY ; Slavin, J ; Henderson, MA (WILEY, 2020-08)
    BACKGROUND AND OBJECTIVES: Leiomyosarcoma of skin (LMS) can be sub-classified on pathology appearances as Dermal or Subcutaneous. The aim of this study was to provide treatment recommendations for these uncommon tumours. METHODS: A retrospective review of all patients with dermal and subcutaneous leiomyosarcoma managed at the Peter MacCallum Cancer Centre, Australia from January 2003 to December 2018 was performed. Eighty-three patients were identified (64 dermal leiomyosarcoma, 19 subcutaneous leiomyosarcoma). RESULTS: Subcutaneous leiomyosarcoma were larger (median size 14 mm dermal, 49 mm subcutaneous, P = 0.01). No patient with a dermal leiomyosarcoma developed metastatic disease compared to 4 of the 19 subcutaneous leiomyosarcoma (5-year overall survivals, 98% and 88%, respectively, P = 0.03). The most common site of metastasis was to the lung. No difference in risk of local recurrence was apparent (5-year recurrence-free survivals were 85% and 78%, respectively, P = 0.17). Adjuvant radiotherapy was used in 16 (25%) dermal leiomyosarcoma patients and 13 (68%) subcutaneous leiomyosarcoma patients (P < 0.001). Local recurrence was uncommon in both tumour subtypes when patients received definitive surgical excision (minimum histological margins of 10 mm as per institutional protocol) regardless of whether radiotherapy was used. The 5-year local recurrence-free survival for dermal leiomyosarcoma treated with radiotherapy was 93% versus 83% without radiotherapy (P = 0.7) and for subcutaneous leiomyosarcoma was 69% and 100%, respectively (P = 0.9). CONCLUSIONS: Dermal leiomyosarcoma have an excellent prognosis, particularly after definitive surgical excision with margins of at least 10 mm. Subcutaneous leiomyosarcoma has poorer outcomes and should be managed by wider excision and considered for adjuvant radiotherapy.
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    Management of pleomorphic dermal sarcoma
    Lonie, S ; Yau, B ; Henderson, M ; Gyorki, D ; Angel, C ; Webb, A (WILEY, 2020-11)
    BACKGROUND: Pleomorphic dermal sarcoma (PDS) is a rare, poorly defined skin neoplasm with features similar to atypical fibroxanthoma, but with adverse histopathological characteristics indicating metastatic potential such as tumour necrosis, invasion beyond superficial subcutis or vascular and/or perineural infiltration. Optimal treatment for PDS is uncertain and reported outcomes vary due to the rarity of this diagnosis and uncertainty over histopathological categorization. The aim of this study was to review the clinical and histopathological features of PDS in a single Australian centre. METHODS: A retrospective review of all patients managed at the Peter MacCallum Cancer Centre with PDS between 2003 and 2017 was performed by a search of electronic records and histories reviewed. RESULTS: A total of 27 patients were identified, mostly elderly males (85.2%, mean age 79.8 years). Lesions were seen most commonly on the head and neck region (96.3%), predominantly on the scalp (63%). Mean tumour radial surgical excision margin was 12.8 mm. Eighteen patients (66.7%) underwent radiotherapy; 13 adjuvant, three neoadjuvant and two with palliative intent. After median follow-up of 46.4 months, two patients had recurrence (7.4%); both had inadequate deep margins at first excision. There were three all-cause deaths in the cohort. There was one disease-specific mortality with metastatic PDS disease at the time of initial presentation. CONCLUSION: PDS is a rare cutaneous malignancy most commonly found in the head and neck region in elderly men, which is best managed with adequate surgical excision. The role of radiotherapy is undefined and an area for future investigation.
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    Identifying challenges to implementation of clinical practice guidelines for sentinel lymph node biopsy in patients with melanoma in Australia: protocol paper for a mixed methods study
    Rapport, F ; Smith, AL ; Cust, AE ; Mann, GJ ; Watts, CG ; Gyorki, DE ; Henderson, M ; Hong, AM ; Kelly, JW ; Long, GV ; Mar, VJ ; Morton, RL ; Saw, RPM ; Scolyer, RA ; Spillane, AJ ; Thompson, JF ; Braithwaite, J (BMJ PUBLISHING GROUP, 2020-02)
    INTRODUCTION: Sentinel lymph node biopsy (SLNB) is a diagnostic procedure developed in the 1990s. It is currently used to stage patients with primary cutaneous melanoma, provide prognostic information and guide management. The Australian Clinical Practice Guidelines state that SLNB should be considered for patients with cutaneous melanoma >1 mm in thickness (or >0.8 mm with high-risk pathology features). Until recently, sentinel lymph node (SLN) status was used to identify patients who might benefit from a completion lymph node dissection, a procedure that is no longer routinely recommended. SLN status is now also being used to identify patients who might benefit from systemic adjuvant therapies such as anti-programmed cell death 1 (PD1) checkpoint inhibitor immunotherapy or BRAF-directed molecular targeted therapy, treatments that have significantly improved relapse-free survival for patients with resected stage III melanoma and improved overall survival of patients with unresectable stage III and stage IV melanoma. Australian and international data indicate that approximately half of eligible patients receive an SLNB. METHODS AND ANALYSIS: This mixed-methods study seeks to understand the structural, contextual and cultural factors affecting implementation of the SLNB guidelines. Data collection will include: (1) cross-sectional questionnaires and semistructured interviews with general practitioners and dermatologists; (2) semistructured interviews with other healthcare professionals involved in the diagnosis and early definitive care of melanoma patients and key stakeholders including researchers, representatives of professional colleges, training organisations and consumer melanoma groups; and (3) documentary analysis of documents from government, health services and non-government organisations. Descriptive analyses and multivariable regression models will be used to examine factors related to SLNB practices and attitudes. Qualitative data will be analysed using thematic analysis. ETHICS AND DISSEMINATION: Ethics approval has been granted by the University of Sydney. Results will be disseminated through publications and presentations to clinicians, patients, policymakers and researchers and will inform the development of strategies for implementing SLNB guidelines in Australia.
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    A survey of surgical management of the sentinel node positive melanoma patient in the post-MSLT2 era
    Downs, JS ; Subramanian, S ; Henderson, MA ; Paton, E ; Spillane, AJ ; Mathy, JA ; Gyorki, DE (WILEY, 2021-12)
    BACKGROUND: The evidence-based management of melanoma patients with a positive sentinel lymph node biopsy (SLNB) has undergone a dramatic shift following publication of practice-changing surgical trials demonstrating no melanoma-specific survival advantage for completion lymph node dissection (CLND) in this scenario. We aimed to survey how surgeons' clinical practice had shifted in response to new evidence from these trials, and at a time when there was starting to become available systemic adjuvant treatments for AJCC Stage III melanoma patients. METHODS: A web-based survey consisting of practice-based questions and hypothetical clinical scenarios about current melanoma practice with regard to positive sentinel node biopsy was developed and sent to the surgical members of a Melanoma and Skin Cancer (MASC) Trials group in December 2018. Responses were analysed using descriptive statistics. RESULTS: There were 212 invitations sent and 65 respondents (31%). Respondents were from 17 countries, 94% of whom practice in specialist melanoma centres or at referral centres. Of these 97% were familiar with the MSLT2 and DeCOG-SLT clinical trials. At survey, 5% of respondents reported routinely recommending CLND and 55% recommend CLND in selected cases. Respondents were most likely to recommend CLND when multiple SLNs were positive. Important factors for surgical decision-making mentioned included size of SLN deposit, number of positive SLNs and likely compliance with the recommended surveillance regimen. CONCLUSION: In line with rapid adoption of published evidence, surgical management of Stage III melanoma has altered significantly, with few surgeons within the cohort now performing routine CLNDs after positive SLNB.