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Background Stereotactic body radiation therapy (SBRT) is an emerging treatment option for liver tumours unsuitable for established curative treatment such as ablation or surgery. The aim of the study is to evaluate the efficacy and safety of SBRT in the treatment of small hepatocellular carcinoma (HCC) in South Australia. Methods From 2014 to 2018, 13 HCC patients were treated with SBRT. Eligibility criteria for SBRT included: unsuitable for standard curative therapies (resection or percutaneous ablation), lack of complete response to prior transarterial chemoembolization, Child-Pugh classification ≤B7, tumours ≤5 cm and minimum of up to 6 months follow-up post-SBRT. The prescribed radiation dose was determined by liver function with doses ranging from 40 to 45 Gy in three or five fractions. Records for all patients were reviewed, and treatment response was scored according to the modified response evaluation criteria in solid tumours. Toxicity was graded according to the Common Terminology Criteria for Adverse Events version 4.0. Results The median follow-up time was 22.7 months, and the median tumour size was 40 mm. The 1 year local control was 92.3%, recurrence-free survival was 67.7% and overall survival was 86.4% at end of study. Three patients underwent liver transplant. No grade ≥3 non-haematological toxicities were observed. One patient experienced acute grade ≥3 haematological toxicity. Conclusion SBRT is a safe, effective and non-invasive alternative treatment option for patients with small HCCs, unsuitable for standard, evidence-based therapies and lacking complete response to transarterial chemoembolization. Randomized controlled trials are required to further investigate the role of SBRT in HCC.

Kerri Beckmann, 1 Sudarshan Selva-Nayagam, 2 Ian Olver, 3 Caroline Miller, 4, 5 Elizabeth S Buckley, 1 Kate Powell, 4 Dianne Buranyi-Trevarton, 6 Raghu Gowda, 7 David Roder, 1 Martin K Oehler 8 1Cancer Epidemiology and Population Health Research, University of South Australia, Adelaide, Australia; 2Medical Oncology, Royal Adelaide Hospital Cancer Centre, Adelaide, Australia; 3Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia; 4South Australian Health and Medical Research Institute, Adelaide, Australia; 5School of Public Health, University of Adelaide, Adelaide, Australia; 6Central Adelaide Local Health Network, SA Health, Adelaide, Australia; 7Radiation Oncology, Royal Adelaide Hospital, Adelaide, Australia; 8Gynaecological Oncology, Royal Adelaide Hospital, Adelaide, AustraliaCorrespondence: Kerri BeckmannCancer Epidemiology and Population Health Research, University of South Australia, Level 8 SAHMRI Building, PO Box 2471 North Terrace, Adelaide, South Australia, AustraliaTel +61 8 83027018Email kerri.beckmann@unisa.edu.auBackground: Uncertainties remain about the most effective treatment for uterine carcinosarcoma (UCS), a rare but aggressive uterine cancer, due to the limited scope for randomized trials. This study investigates whether nodal excision or adjuvant therapies after hysterectomy offer a survival benefit, using multi-institutional clinical registry data from South Australia.Methods: Data for all consecutive cases of UCS from 1980 to 2019 were extracted from the Clinical Cancer Registry. Clinical and treatment-related factors associated with disease-specific mortality (DSM) and all-cause mortality (ACM) were determined using multivariable Cox proportional hazards regression, with subgroup analyses by stage.Results: Median follow-up for the 140 eligible cases was 21 months. 94% underwent hysterectomy, and 72% had an additional pelvic lymph node dissection (PLND). Furthermore, 16% received adjuvant chemotherapy; 11% adjuvant radiotherapy and 16% multimodal chemoradiotherapy, with an increase in the latter two modalities over time. DSM was reduced among those who underwent PLND (HR: 0.41; 95%CI: 0.23– 0.74), adjuvant chemotherapy (HR: 0.39; 95%CI: 0.18– 0.84) or multimodality treatment (HR: 0.11; 95%CI: 0.06– 0.30) compared with hysterectomy alone for the whole cohort and for late stage disease (FIGO III/IV) but not for earlier stage disease, except for reduced DSM with multimodal therapy. Findings were similar for ACM.Conclusion: Our findings indicate better survival among those who received PLND, chemotherapy and multimodal adjuvant therapy, with the latter applying to early and late stage disease. However, cautious interpretation is warranted, due to potential “indication bias” and limited power. Further research into effective treatment modalities, ideally using prospective study designs, is needed.Keywords: uterine carcinosarcoma, management, survival, multimodal therapy, adjuvant chemotherapy, adjuvant radiotherapy

A new analysis method for the rtOSL of BeO ceramics is presented, using temporal curve fitting of an expected rtOSL signal to measured rtOSL signals. The presented technique does not require heavy signal averaging to determine the OSL bleaching correction associated with the rtOSL method, reducing uncertainties in the post-correction rtOSL. The corrected rtOSL signal was demonstrated to be linear with dose, and dose-rate independent. The presented technique is expected to be applicable for many other dosimeters capable of the rtOSL technique. The presented technique achieved relative uncertainties in the corrected rtOSL between 3.4% and 6.5%. The initial measurements are promising, but uncertainties are required to be further improved upon before the technique can be used clinically. Refereed/Peer-reviewed

Introduction The role and timing of postoperative radiotherapy (PORT) in the management of retroperitoneal sarcoma (RPS) remains controversial. Method This is a retrospective cohort review of patients undergoing curative resection for RPS at a single institution between January 2011 and July 2016. Patient selection was through the South Australian Soft Tissue Tumour Multidisciplinary Group (MDT) based at Royal Adelaide Hospital. An individualised approach, including assessment of resectability, histopathological grade and subtype, and radiotherapy considerations, was taken for each patient. Patients offered preoperative radiotherapy or palliation were excluded. A saline-filled spacer was inserted following operative resection. Radiotherapy commenced postoperatively. Patients underwent laparotomy to remove the device approximately 6 weeks post completion of PORT. Primary endpoints were technical feasibility, perioperative morbidity and radiation toxicity. Secondary endpoints were local recurrence (LR), distant recurrence (DR) and death. Results During the study period, 40 patients with RPS were managed through the MDT. Twelve patients (ages 33–78) underwent PORT utilising spacers. Radiotherapy toxicity was reported in four patients and extensive adhesions observed in another four patients during spacer removal. Median follow-up was 35 months (range 4–60). Seven patients remain alive and disease free. Four patients developed LR, three developed DR. Three patients died; two with DR and one with LR. Two patients with recurrent/progressive disease are alive; one with DR and one with LR. Conclusion Use of intraoperative spacers to facilitate PORT is feasible, with acceptable toxicity following resection of RPS. Patient selection for this approach remains to be determined.

The purpose of this study was to investigate the potential of real-time optically stimulated luminescence (rtOSL) measurements of a beryllium oxide (BeO) ceramic fibre-coupled luminescence dosimetry system. By pulsing the stimulation laser during the exposure to ionizing radiation, an rtOSL dose-rate measurement can be obtained which could be stem effect free. A portable rtOSL BeO ceramic fibre-coupled dosimetry system is presented and characterized using a constant dose-rate superficial 140 kVp X-ray beam. The rtOSL was measured for dose-rates between 0.29 and 3.88 Gy/min, controlled by varying the source to surface distance. After correcting for OSL decay during the exposure, a linear dose-rate response of the change in rtOSL (ΔrtOSL) was observed. The ΔrtOSL was also observed to be stem effect free. Refereed/Peer-reviewed

Therapy-related myeloid neoplasms (T-MN) are poorly characterized secondary hematological malignancies following chemotherapy/radiotherapy exposure. We compared the clinical and mutational characteristics of T-MN (n = 129) and primary myelodysplastic syndrome (P-MDS, n = 108) patients. Although the somatic mutation frequency was similar between T-MN and P-MDS patients (93% in both groups), the pattern was distinct. TP53 mutations were more frequent in T-MN (29.5 vs. 7%), while spliceosomal complex mutations were more common in P-MDS (56.5 vs. 25.6%). In contrast to P-MDS, the ring sideroblasts (RS) phenotype was not associated with better survival in T-MN, most probably due to genetic association with TP53 mutations. SF3B1 was mutated in 96% of P-MDS with ≥15% RS, but in only 32% T-MN. TP53 mutations were detected in 92% T-MN with ≥15% RS and SF3B1 wild-type cases. Interestingly, T-MN and P-MDS patients with “Very low” or “Low” Revised International Prognostic Scoring System (IPSS-R) showed similar biological and clinical characteristics. In a Cox regression analysis, TP53 mutation was a poor prognostic factor in T-MN, independent of IPSS-R cytogenetics, disease-modifying therapy, and NRAS mutation. Our data have direct implications for T-MN management and provide evidence that, in addition to conventional disease parameters, mutational analysis should be incorporated in T-MN risk stratification Refereed/Peer-reviewed

Therapy-related myeloid neoplasms (T-MN) are poorly characterized secondary hematological malignancies following chemotherapy/radiotherapy exposure. We compared the clinical and mutational characteristics of T-MN (n = 129) and primary myelodysplastic syndrome (P-MDS, n = 108) patients. Although the somatic mutation frequency was similar between T-MN and P-MDS patients (93% in both groups), the pattern was distinct. TP53 mutations were more frequent in T-MN (29.5 vs. 7%), while spliceosomal complex mutations were more common in P-MDS (56.5 vs. 25.6%). In contrast to P-MDS, the ring sideroblasts (RS) phenotype was not associated with better survival in T-MN, most probably due to genetic association with TP53 mutations. SF3B1 was mutated in 96% of P-MDS with ≥15% RS, but in only 32% T-MN. TP53 mutations were detected in 92% T-MN with ≥15% RS and SF3B1 wild-type cases. Interestingly, T-MN and P-MDS patients with "Very low" or "Low" Revised International Prognostic Scoring System (IPSS-R) showed similar biological and clinical characteristics. In a Cox regression analysis, TP53 mutation was a poor prognostic factor in T-MN, independent of IPSS-R cytogenetics, disease-modifying therapy, and NRAS mutation. Our data have direct implications for T-MN management and provide evidence that, in addition to conventional disease parameters, mutational analysis should be incorporated in T-MN risk stratification.

Registry data on invasive cervical cancers (n = 1,274) from four major hospitals (1984-2012) were analysed to determine their value for informing local service delivery in Australia. The methodology comprised disease-specific survival analyses using Kaplan-Meier product-limit estimates and Cox proportional hazards models and treatment analyses using logistic regression. Five- and 10-year survivals were 72% and 68%, respectively, equating with relative survival estimates for Australia and the USA. Most common treatments were surgery and radiotherapy. Systemic therapies increased in recent years, generally with radiotherapy, but were less common for residents from less accessible areas. Surgery was more common for younger women and early-stage disease, and radiotherapy for older women and regional and more advanced disease. The proportion of glandular cancers increased in-step with national trends. Little evidence of variation in risk-adjusted survival presented over time or by Local Health District. The study illustrates the value of local registry data for describing local treatment and outcomes. They show the lower use of systemic therapies among residents of less accessible areas which warrants further investigation. Risk-adjusted treatment and outcomes did not vary by socio-economic status, suggesting equity in service delivery. These data are important for local evaluation and were not available from other sources. Refereed/Peer-reviewed

Approximately 8% of un-selected pediatric (Zhang et al, NEJM 2015) and adult (Huang et al, Cell 2018) cancer patients have a deleterious germline (GL) variant. However, the frequency in patients with >2 non-related cancers, a combination of different hematological malignancies (HM) or a HM and a non-hematological malignancy, is not known. We hypothesize that genetic predisposition is higher in patients with multiple cancers, compared to historical literature for patients with a single cancer. Method: Clinical and laboratory information on 213 cancer patients, enrolled in the South Australian MDS (SA-MDS) registry (n=90) and University of Chicago clinic (n=123) were analyzed. Germline variants were identified by sequencing paired bone marrow and germline samples for 217-300 cancer related genes and annotated using American College of Medical Genetics (ACMG) 2015 guidelines as pathogenic or likely pathogenic (i.e. deleterious). Additionally, somatic mutations in 240 genes were identified in the SA-MDS cohort (n=90). Results: The median age at diagnosis was 64 years (interquartile range, 61-76 years). One-hundred and five patients had therapy-related myeloid neoplasm (T-MN), following treatment with chemo- and/or radiotherapy for an unrelated prior malignancy. While 100 patients had non-related multiple cancers (MC) one of them being HM without prior exposure to chemotherapy or radiotherapy, and, 8 patients had only myelodysplastic syndrome or acute myeloid leukemia. Overall, 20.5% (42/205) patients harbored 46 deleterious GL variants, annotated according to ACMG guidelines (Fig 1A). Most GL variants were in DNA repair pathway (26/46, 57%) followed by TP53, telomere maintenance and drug transport pathways (4/46, 9% each; Fig 1B). Three DDX41 variants were also seen. The frequency of patients with deleterious GL variants was similar in T-MN (21/105; 20%) and MC (21/100, 21%; Fig 1C). Similarly, the frequency of patients with deleterious GL variants in DNA repair pathways was also similar in T-MN (13/105, 12%) and MC (11/100, 11%). Of the patients with available cytogenetic data, complex cytogenetics were more frequent in patients with a deleterious GL variant compared to those without (11/28, 39% vs 28/125, 22%; p=0.06). At the time of analysis, somatic and germline mutation data on 240 genes was available in the SA-MDS cohort only (n=90). Somatic TP53 mutations were frequent in patients with deleterious GL variant (8/15, 53%) compared to patients without deleterious GL variant (11/75, 15%; p=0.003) (Fig 1D). Interestingly, 80% (4/5) patients with deleterious GL variant in a DNA repair pathway had a somatic TP53 mutation compared to 40% (4/10) with deleterious GL variant in non-DNA repair pathways. Conclusions: Our results from a large cohort show that patients with >2 non-related cancers have a higher frequency of deleterious germline variants compared to previous reports from patients with single cancer (20.5% vs 8%). Variants in the DNA repair pathway are the most common. The presence of deleterious germline variants is associated with genetic instability as evidenced by high frequency of complex karyotypes and somatic TP53 mutations. Disclosures Scott: Celgene: Honoraria. Godley:UpToDate, Inc.: Patents & Royalties: receives royalties from a coauthored article on inherited hematopoietic malignancies ; Invitae, Inc.: Membership on an entity's Board of Directors or advisory committees.

Postimplant dosimetry (PID) after Iodine-125 (125I) implant of the prostate should offer a reliable qualitative assessment. So far, there is no consensus regarding the optimum PID method, though the latest literature is in favor of magnetic resonance imaging (MRI). This study aims to simultaneously compare 3 PID techniques: (1) MRI-computed tomography (CT) fusion; (2) ultrasound (US)-CT fusion; and (3) manual target delineation on CT. The study comprised 10 patients with prostate cancer. CT/MR scans with urinary catheters in place for PID were done either on day 0 or day 1 postimplantation. The main parameter evaluated and compared among methods was target D90. The results show that CT-based D90s are lower than US-CT D90s (median difference,-6.85%), whereas MR-CT PID gives higher D90 than US-CT PID (median difference, 4.25%). Manual contouring on CT images tends to overestimate the prostate volume compared with transrectal ultrasound (TRUS) (median difference, 23.33%), whereas on US images the target is overestimated compared with MR-based contouring (median difference, 13.25%). Although there are certain differences among the results given by various PID techniques, the differences are statistically insignificant for this small group of patients. Any dosimetric comparison between 2 PID techniques should also account for the limitations of each technique, to allow for an accurate quantification of data. Given that PID after permanent radioactive seed implant is mandatory for quality assurance, any imaging method-based PID (MR-CT, US-CT, and CT) available in a radiotherapy department can be indicative of the quality of the procedure. Refereed/Peer-reviewed

Oesophageal cancer is a relatively uncommon malignancy, but with poor prognosis. Despite several treatment options that are available, the 5-year survival rates rarely exceed 40%. This review discusses the main challenges of oesophageal cancer, the available treatment options, and the most effective treatment in terms of overall survival. The outcomes of clinical trials show that neo-adjuvant chemo-radiotherapy using cisplatin and 5-fluorouracil followed by oesophagectomy results in the greatest survival. However, the optimal chemotherapy and radiotherapy schedule remains unclear. There is no satisfactory treatment to date, particularly for patients with co-morbidities or advanced tumours. Refereed/Peer-reviewed

Background: The worldwide incidence of esophageal cancer has greatly increased over the past few decades making it the sixth deadliest cancer. The disease is often detected in advanced stages when surgery is no longer an option. The standard treatment in these situations is combined chemoradiotherapy, by employing drug cocktails that lead to optimal treatment outcomes both from the perspective of tumor control and normal tissue toxicity. Methods: The aim of this work was to collate the existing trials and clinical studies reported on non-operable esophageal cancer and to analyze the results based on treatment outcomes after various drug combinations. Results: Of all drug combinations, cisplatin/5-FU is the most well established chemotherapy regimen for esophageal cancer as both neoadjuvant therapy, an alternative option to surgery, and for palliative purposes. Although this regimen is associated with the most toxicity, it also appears to have the best survival benefit and relief of symptoms. Conclusions: More research is warranted to further increase the therapeutic ratio in non-operable esophageal cancers.

Background There is a paucity of data on the current management of patients with advanced soft tissue sarcoma (STS) in the Australian health care setting. This study utilised the Australian sarcoma database to evaluate the patterns of care delivered to patients with advanced STS at Australian sarcoma services. Methods Prospectively collected data from six sarcoma centres in Australia were sourced to identify patients diagnosed with advanced STS between 1 January 2010 and 31 December 2012. Descriptive statistics were analysed for patient demographics, clinicopathological characteristics and treatment patterns. Overall survival was estimated using the Kaplan–Meier product limit method. Results Of 253 patients with advanced STS, four major STS subtypes were identified: undifferentiated pleomorphic sarcoma (23 %), leiomyosarcoma (17 %), liposarcoma (14 %), and synovial sarcoma (8 %); with the rest grouped as “other STS” (38 %). Approximately one-third of patients received palliative systemic therapy with the most common first-line therapy being doxorubicin alone (50 %). A small percentage of patients participated in clinical trials (20 %). Palliative radiotherapy was utilised mostly for treatment of symptomatic distant metastases and one-third of patients underwent metastasectomy, most commonly for pulmonary metastases. The median overall survival (OS) in this series was 18 months and no significant difference in OS was observed across different STS histological subtypes. Conclusions This is the first detailed study outlining patterns of care for Australian patients with advanced STS managed at sarcoma services. These data highlight a particular area of weakness in the lack of clinical trials for sarcoma patients and also serve as an important reference point for understanding how practice may change over time as treatment options evolve.

Purpose: The roles of postimplant dosimetry (PID) after permanent I-125 implant are to identify and rectify inadequate implants, assess the dosimetric quality indicators, and evaluate dose to the organs at risk. The aim of the current work was to assess the progress of prostate implant quality via postimplant dosimetry over seven years. Methods : The following factors were investigated to assess the PID results obtained over seven years: the improvement in implant technique, the computed tomography(CT) delineation-based PID versus ultrasound-CT (US-CT) fusion-based PID, and the evolution of parameters such as D90 and NDR (natural dose ratio). The correlation between dosimetric parameters and clinical outcomes were also evaluated. Results : The seven years PID learning curve shows clear changes in dosimetric trend for the 265 patients studied. Manual target contouring on CT was shown to overestimate the prostate volume when compared to ultrasound data, translating to CT-based D90 values being lower than US-CT D90. It was found that NDR does not contribute with additional dosimetric information to postimplant dosimetry evaluation. Patient follow-up data show that 4.7% patients have relapsed, and urinary retention was reported in 2.7% of the patients. Conclusions : CT-based PID was found less reliable than US-CT fusion-based PID due to target volume overestimation. This result shows the biased interpretation of low D90 values based on CT-based targeting, providing unreliable correlations between D90 and relapse probability. The low urinary retention statistics are in accordance with the PID data for the organ, as only 5.2% of patients had their PID D10 > 218 Gy, i.e., above the recommended GEC-ESTRO guidelines. Besides the “learning” component, the PID D90 curve is influenced by the PID technique.

This paper reviews the logic and dimensional analysis results leading up to correlation equations for parachute opening time, including the effects of canopy stiffness. An earlier expression for effective canopy stiffness is modified by leaving out the Poisson’s ratio term, and also expressing the equation in terms of dynamic pressure. The procedure described simplifies techniques previously developed and gives a more practical correlation formula. Other applications of the stiffness index are suggested, and an illustration is given for its use in tented structures.

The roles of postimplant dosimetry (PID) after permanent I-125 implant are to identify and rectify inadequate implants, assess the dosimetric quality indicators, and evaluate dose to the organs at risk. The aim of the current work was to assess the progress of prostate implant quality via postimplant dosimetry over seven years.The following factors were investigated to assess the PID results obtained over seven years: the improvement in implant technique, the computed tomography (CT) delineation-based PID versus ultrasound-CT (US-CT) fusion-based PID, and the evolution of parameters such as D90 and NDR (natural dose ratio). The correlation between dosimetric parameters and clinical outcomes were also evaluated.The seven years PID learning curve shows clear changes in dosimetric trend for the 265 patients studied. Manual target contouring on CT was shown to overestimate the prostate volume when compared to ultrasound data, translating to CT-based D90 values being lower than US-CT D90. It was found that NDR does not contribute with additional dosimetric information to postimplant dosimetry evaluation. Patient follow-up data show that 4.7% patients have relapsed, and urinary retention was reported in 2.7% of the patients.CT-based PID was found less reliable than US-CT fusion-based PID due to target volume overestimation. This result shows the biased interpretation of low D90 values based on CT-based targeting, providing unreliable correlations between D90 and relapse probability. The low urinary retention statistics are in accordance with the PID data for the organ, as only 5.2% of patients had their PID D10218 Gy, i.e., above the recommended GEC-ESTRO guidelines. Besides the "learning" component, the PID D90 curve is influenced by the PID technique.

This paper describes a novel project that is being used to educate aerospace engineering students in the technique of parasite drag coefficient estimation. The project is conducted on a wing-body-tail configuration using the method of wetted areas. The wing-body-tail is actually a miniature two-man submarine, but the techniques used are identical to an airplane. Also included in the project are propeller performance estimation and determining the power required to overcome parasite drag. The students compare their results with empirical data. The project is interdisciplinary in nature, in that it can also be used in ocean engineering courses for submarine drag estimation.

Varicella-zoster virus can cause neurological disease in primary and reactivated latent forms, with a wide spectrum of disorders throughout a person’s lifetime. 35-year-old male with AIDS; histoplasmosis; mild, intermittent asthma; and hypertension presented to hospital with left-sided weakness and slurred speech. Exam showed left hemiparesis with left upper motor neurons facial palsy and dysarthria. Acute right basal ganglia infarct was detected in head CT without contrast. A subsequent MRI showed acute non-hemorrhagic infarct, right basal ganglia; fusiform dilatation, and proximal right middle cerebral artery. A CT angiogram of the bilateral carotid arteries revealed occlusion of the right anterior cerebral artery with conical dilatation at the origin; significant stenosis, and dilatation of the right middle cerebral artery. These findings were consistent with vasculitis. Patient was successfully treated with IV acyclovir. Rapid diagnosis of VZV vasculopathy is important because it is a treatable cause of stroke. Mortality rate is 25% without treatment.