Sir Peter MacCallum Department of Oncology - Research Publications

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    Systemic treatments and outcomes in CIC-rearranged Sarcoma: A national multi-centre clinicopathological series and literature review
    Connolly, EA ; Bhadri, VA ; Wake, J ; Ingley, KM ; Lewin, J ; Bae, S ; Wong, DD ; Long, AP ; Pryor, D ; Thompson, SR ; Strach, MC ; Grimison, PS ; Mahar, A ; Bonar, F ; Maclean, F ; Hong, A (WILEY, 2022-02-17)
    UNLABELLED: CIC-rearranged sarcoma is a recently established, ultra-rare, molecularly defined sarcoma subtype. We aimed to further characterise clinical features of CIC-rearranged sarcomas and explore clinical management including systemic treatments and outcomes. METHODS: A multi-centre retrospective cohort study of patients diagnosed between 2014-2019. RESULTS: Eighteen patients were identified. The median age was 27 years (range 13-56), 10 patients were male (56%), 11 patients (61%) had localised disease and 7 patients had advanced (metastatic or unresectable) disease at diagnosis. Of 11 patients with localised disease at diagnosis, median overall survival (OS) was 40.6 months and the 1-, 2- and 5-year OS estimates were 82%, 64% and 34% respectively. Nine patients (82%) underwent surgery (all had R0 resections), 8 (73%) patients received radiotherapy to the primary site (median dose 57Gy in 28 fractions), and 8 (73%) patients received chemotherapy (predominantly Ewing-based regimens). Metastases developed in 55% with a median time to recurrence of 10.5 months. In patients with advanced disease at diagnosis, median OS was 12.6 months (95% CI 5.1-20.1), 1-year OS was 57%. Median progression-free survival was 5.8 months (95% CI 4.5-7.2). Durable systemic therapy responses occurred infrequently with a median duration of systemic treatment response of 2.1 months. One durable complete response of metastatic disease to VDC/IE chemotherapy was seen. Responses to pazopanib (n = 1) and pembrolizumab (n = 1) were not seen. CONCLUSION: In this series, CIC-rearranged sarcomas affected young adults and had a high incidence of presenting with, or developing, metastatic disease. The prognosis overall was poor. In advanced disease, durable systemic therapy responses were infrequent.
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    Treatment of patients with primary retroperitoneal sarcoma: predictors of outcome from an Australian specialist sarcoma centre
    Snow, HA ; Hitchen, TX ; Head, J ; Herschtal, A ; Bae, S ; Chander, S ; Chu, J ; Hendry, S ; Ngan, SY ; Desai, J ; Choong, PFM ; Henderson, M ; Gyorki, DE (WILEY, 2018-11-01)
    BACKGROUND: Several unanswered questions surround the management of retroperitoneal sarcoma (RPS). Guidelines recommend treatment by a multidisciplinary team at a specialized referral centre. The objective of this study was to describe the management of RPS at an Australian specialist sarcoma centre, comparing outcomes to international standards and analysing for predictors of local failure. METHODS: A retrospective review of a prospectively maintained database was performed on patients with RPS treated between 2008 and 2016. A 5-year outcome analyses focussed on patients undergoing curative-intent surgery for primary, non-metastatic RPS. RESULTS: Eighty-eight patients underwent surgery for primary RPS. Five-year overall survival was 66%, 5-year freedom from local recurrence was 65% and 5-year freedom from distant metastasis was 71%. Overall survival was associated with tumour grade (hazard ratio (HR) 6.1, P < 0.001) and histologic organ invasion (HR 5.7, P < 0.001). Variables associated with improved freedom from local recurrence were macroscopically complete resection (HR 0.14, P < 0.001) and neoadjuvant radiotherapy (HR 0.33, P = 0.014). Treatment at a specialist sarcoma centre was associated with a higher rate of preoperative biopsy and neoadjuvant radiotherapy (both with P < 0.001). There was a trend towards improved local control for patients undergoing surgery at a specialist centre (P = 0.055). CONCLUSION: This is the largest Australian series of RPS and outcomes are comparable to major international sarcoma centres. Patients treated at a specialist centre had higher rates of preoperative diagnosis and tailored therapy which was associated with improved outcomes. Patients with suspected RPS should be referred to a specialist centre for optimal preoperative evaluation and multidisciplinary management.
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    Patterns of care of superficial soft tissue sarcomas: it is not always just a lump
    Le Tan, MT ; Thompson, SR ; Schipp, D ; Bae, S ; Crowe, PJ (WILEY, 2018-10-01)
    AIM: Superficial soft tissue sarcomas (S-STS) are generally considered low-risk tumors and have an excellent prognosis when treated with appropriate surgery and adjuvant therapy. However, they are often misdiagnosed then mistreated, leading to significant morbidity. This study aims to examine the patterns of care and outcomes of patients with S-STS, comparing those initially managed through sarcoma units versus elsewhere. METHODS: Patients with S-STS from Prince of Wales Hospital in NSW (1995-2013) and Peter MacCallum Cancer Centre in Victoria (2009-2013) were identified from a national sarcoma database. Baseline variables, treatment and disease outcomes were recorded. Statistical tests performed included univariate and multivariate analyses, chi-square tests, as well as the Kaplan-Meier method for 5-year local recurrence and survival rates. RESULTS: Eighty-nine patients were identified, with 35% initially managed at a sarcoma unit and 65% elsewhere. Patients initially managed at sarcoma units had larger tumors (>5 cm 39% vs 17%; P  =  0.036) with a trend to higher grade (61% vs 48%; P = 0.39). Patients that were initially managed outside a sarcoma unit more often underwent open surgical biopsies (P < 0.0005), had multiple operations (P < 0.0005) and had higher rates of local recurrences (24% vs 6.5%, P  =  0.038). They also had lower 5-year local recurrence-free survival rates (P = 0.022), but had higher metastasis-free survival (P = 0.014). On multivariate analysis, only larger STS size and male gender predicted for poorer metastasis-free survival (P = 0.042 and 0.018, respectively). CONCLUSION: Patients with S-STS initially managed outside specialized sarcoma units undergo more operations, with risk of greater morbidity, and have greater risk of local recurrence.
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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, 2020-10-20)
    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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    CART-WHEEL.org: An Ethically Approved Online Database for Patient-Entered Data to Facilitate Rare Cancer Research
    Kee, D ; Parker, C ; Bae, S ; Tucker, KM ; Harrison, M ; Tohidi-Esfahani, I ; Black, M ; Delahunty, R ; Ananda, S ; Friedlander, M ; Cunliffe, HE ; Gibbs, P ; Desai, J ; Trotman, J ; Scott, CL (LIPPINCOTT WILLIAMS & WILKINS, 2020-02-21)
    PURPOSE: Rare cancers are challenging for researchers, as clinicians and scientists have difficulty recruiting sufficient patient cases to power studies appropriately. Likewise, patients often are frustrated by a lack of specific information or evidence base for their cancer and, although eager to participate in research, have limited opportunities. We established CART-WHEEL.org, an online patient-entered database, to directly engage patients in the research process, collect rare cancer data, and facilitate their entry into additional research. PATIENTS AND METHODS: Patients access CART-WHEEL.org directly online. Clinical information is collected from users via a streamlined questionnaire developed collaboratively with consumer groups to ensure accessibility and relevance. Data collected include the following: patient demographics, comorbidities, and risk factors and tumor diagnostic, biomarker, and treatment history. Patients can download a medical summary for personal use; consent for research use of data; and indicate willingness to be contacted about other research or clinical trials. We describe data collected to date and its validation, and we provide examples of how CART-WHEEL.org can facilitate rare cancer research. RESULTS: From January 2010 to March 2018, 558 patients provided consent and entered their rare cancer data. One hundred distinct rare tumor types and patients from 22 countries were included. Validation of data entered by 21 patients with sarcoma against a hospital database demonstrated accuracy sufficient to facilitate future research in key fields, such as tumor site (95%) and histopathologic diagnosis (90%). Examples of CART-WHEEL-based disease-specific projects, subsequent recruitment to other rare cancer projects, and rare cancer patient cases of interest are described. CONCLUSIONS: Online platforms like CART-WHEEL.org can engage consumers directly, facilitating collection of patient-entered rare cancer data for hypothesis generation, and connect patients with researchers to enable specific rare cancer research and clinical trials.
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    Cost-effectiveness analysis of imaging surveillance in stage II and III extremity soft tissue sarcoma: an Australian perspective
    Bae, S ; Karnon, J ; Crane, G ; Bessen, T ; Desai, J ; Crowe, P ; Neuhaus, S (BMC, 2020-02-03)
    BACKGROUND: Surveillance imaging is used to detect local and/or distant recurrence following primary treatment of localised soft tissue sarcoma (STS), however evidence supporting optimal surveillance modality or frequency is lacking. We used prospectively collected sarcoma data to describe current surveillance imaging practice in patients with AJCC stage II and III extremity STS and evaluate its cost-effectiveness. METHODS: From three selected Australian sarcoma referral centres, we identified patients with stage II and III extremity STS treated between 2009 and 2013. Medical records were reviewed to ascertain surveillance imaging practices, including modality, frequency and patient outcomes. A discrete event simulation model was developed and calibrated using clinical data to estimate health service costs and quality adjusted life years (QALYs) associated with alternative surveillance strategies. RESULTS: Of 133 patients treated for stage II and III extremity STS, the majority were followed up with CT chest (86%), most commonly at 3-monthly intervals and 62% of patients had the primary site imaged with MRI at 6-monthly. There was limited use of chest-X-ray. A discrete event simulation model demonstrated that CT chest screening was the most cost effective surveillance strategy, gaining additional QALYs at a mean incremental cost of $30,743. MRI alone and PET-CT alone were not cost-effective, whilst a combined strategy of CT + MRI had an incremental cost per QALY gained of $96,556. CONCLUSIONS: Wide variations were observed in surveillance imaging practices in this high-risk STS cohort. Modelling demonstrated the value of CT chest for distant recurrence surveillance over other forms of imaging in terms of cost and QALYs. Further work is required to evaluate cost-effectiveness in a prospective manner.