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Background: Concurrent chemoradiotherapy (CRT) with cisplatin is a widely accepted treatment strategy for patients with LA HNSCC. However, some patients are deemed Cisplatin ineligible for a variety of reasons and offered alternative sensitising agents. There is a paucity of data regarding outcomes in patients treated with non-cisplatin chemotherapy. Patients and Methods: We retrospectively analysed all consecutive adult LA HNSCC patients from January 2016-Feb 2020 treated with chemoradiotherapy in the definitive or adjuvant settings.We collected data on patient and tumour characteristics, chemotherapy regimen, toxicity as well as clinical outcomes including locoregional control and survival. Result(s): Over the 4-year period, a total of 194 patients received CRT for LA HNSCC. Median age was 61 years (range: 22-82) with a male/female ratio of 6:1. Primary tumour site was the oropharynx in 161 (83%), hypopharynx in 12 (6%), oral cavity in 11 (6%) and larynx in 9 (5%) patients. P16 positive tumours accounted for 146 (75%) of all tumours. Most patients (174, 90%) had definitive treatment as opposed to adjuvant therapy (20, 10%). Cisplatin based chemotherapy was employed in 154 (80%) of all patients, and non-cisplatin-based treatment in 44 (20%). Carboplatin plus paclitaxel was used in 21 (11%) and Cetuximab in 15 (8%) of the entire patient cohort. Carboplatin alone in the adjuvant setting was used in 3 (1%) patients. Final survival and toxicity data will be reported at the conference. Conclusion(s):Non-cisplatin-based chemotherapy was used in20%of our patient cohort with LA HNSCC. It is important to ascertain the safety and efficacy data in these two groups of patients treated with radical CRT.

Amplifications of the androgen receptor (AR) occur in up to 80% of men with castration-resistant prostate cancer (CRPC). Recent studies highlighted that these amplifications not only span the AR gene but usually encompass a distal enhancer. This represents a newly recognised, non-coding mechanism of resistance to AR-directed therapies, including enzalutamide. To study disease progression before and after AR amplification, we used tumour samples from a castrate-sensitive primary tumour and castrate-resistant metastasis of the same patient. For subsequent functional and genomic studies, we established serially transplantable patient-derived xenografts (PDXs). Whole genome sequencing showed that alterations associated with poor prognosis, such as TP53 and PTEN loss, existed before androgen deprivation therapy, followed by co-amplification of the AR gene and enhancer after the development of metastatic CRPC. The PDX of the primary tumour, without the AR amplification, was sensitive to AR-directed treatments, including castration, enzalutamide, and apalutamide. The PDX of the metastasis, with the AR amplification, had higher AR and AR-V7 expression in castrate conditions, and was resistant to castration, apalutamide, and enzalutamide in vivo. Treatment with a BET inhibitor outperformed the AR-directed therapies for the metastasis, resulting in tumour regression for some, but not all, grafts. Therefore, this study provides novel matched PDXs to test potential treatments that target the overabundance of AR in tumours with AR enhancer amplifications. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Aims: To utilise real-time patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs) to better understand the symptoms and concerns of patients attending an oncology outpatient clinic. Method(s): Patients were invited to complete a suite of PROMs and PREMs including the EQ-5D-5L, modified Edmonton Symptom Assessment System-Revised (ESAS-R) and the modified Supportive Care Needs Survey Short-Form (SCNS-SF34) on an iPad immediately before each appointment. Descriptive statistics were reported for the PROMs and PREMs. SCNS-SF34 domain Likert scores were summated and then standardised. Multiple linear regression was conducted to determine predictors of self-rated health (EQ-VAS score) with age, cancer type, tumour stage, treatment intent, current treatment, treatment modality and, cancer recurrence. Result(s): Of 146 patients approached, 100 patients (68.5%) participated (99 females, mean age 60.7 years). Primary cancer diagnoses were breast (67%), gynaecological (31%) and lung (2%) cancers. Patients speaking a language other than English were less likely to participate (73% vs 36%, P = .01). Median self-rated health (EQ-VAS score) among participants was 74/100 (IQR 32.5). No clinical or demographic factors were independently associated with self-rated health, P > .05. Only 8% of participants reported no problems on any dimension of the EQ-5D-5L. The top 3 symptom concerns (ESAS-R score >=7) were tiredness (33.0%), sleep problems (24.5%) and drowsiness (21.2%). The SCNS-SF34 domains of greatest unmet need were psychological (median 45, IQR 42.1) and physical (median 40, IQR 46.3). Conversely, the domain of lowest unmet need was sexuality (median 16.7, IQR 33.3). Conclusion(s): These data reflect the symptoms and concerns impacting on quality of life among real-world oncology patients in the immediate pre-COVID era. Findings will facilitate targeted supportive care interventions to those in greatest need. The project will be adapted for r

Background: Concurrent chemoradiotherapy (CRT) with cisplatin is a widely accepted treatment strategy for patients with LA HNSCC. However, some patients are deemed Cisplatin ineligible for a variety of reasons and offered alternative sensitising agents. There is a paucity of data regarding outcomes in patients treated with non-cisplatin chemotherapy. Patients and Methods: We retrospectively analysed all consecutive adult LA HNSCC patients from January 2016-Feb 2020 treated with chemoradiotherapy in the definitive or adjuvant settings.We collected data on patient and tumour characteristics, chemotherapy regimen, toxicity as well as clinical outcomes including locoregional control and survival. Result(s): Over the 4-year period, a total of 194 patients received CRT for LA HNSCC. Median age was 61 years (range: 22-82) with a male/female ratio of 6:1. Primary tumour site was the oropharynx in 161 (83%), hypopharynx in 12 (6%), oral cavity in 11 (6%) and larynx in 9 (5%) patients. P16 positive tumours accounted for 146 (75%) of all tumours. Most patients (174, 90%) had definitive treatment as opposed to adjuvant therapy (20, 10%). Cisplatin based chemotherapy was employed in 154 (80%) of all patients, and non-cisplatin-based treatment in 44 (20%). Carboplatin plus paclitaxel was used in 21 (11%) and Cetuximab in 15 (8%) of the entire patient cohort. Carboplatin alone in the adjuvant setting was used in 3 (1%) patients. Final survival and toxicity data will be reported at the conference. Conclusion(s):Non-cisplatin-based chemotherapy was used in20%of our patient cohort with LA HNSCC. It is important to ascertain the safety and efficacy data in these two groups of patients treated with radical CRT.

Amplifications of the androgen receptor (AR) occur in up to 80% of men with castration-resistant prostate cancer (CRPC). Recent studies highlighted that these amplifications not only span the AR gene but usually encompass a distal enhancer. This represents a newly recognised, non-coding mechanism of resistance to AR-directed therapies, including enzalutamide. To study disease progression before and after AR amplification, we used tumour samples from a castrate-sensitive primary tumour and castrate-resistant metastasis of the same patient. For subsequent functional and genomic studies, we established serially transplantable patient-derived xenografts (PDXs). Whole genome sequencing showed that alterations associated with poor prognosis, such as TP53 and PTEN loss, existed before androgen deprivation therapy, followed by co-amplification of the AR gene and enhancer after the development of metastatic CRPC. The PDX of the primary tumour, without the AR amplification, was sensitive to AR-directed treatments, including castration, enzalutamide, and apalutamide. The PDX of the metastasis, with the AR amplification, had higher AR and AR-V7 expression in castrate conditions, and was resistant to castration, apalutamide, and enzalutamide in vivo. Treatment with a BET inhibitor outperformed the AR-directed therapies for the metastasis, resulting in tumour regression for some, but not all, grafts. Therefore, this study provides novel matched PDXs to test potential treatments that target the overabundance of AR in tumours with AR enhancer amplifications. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

BACKGROUND Leukocytes, such as T cells and macrophages, play an important role in tumorigenesis. CC chemokine ligand (CCL) 4, which is produced by lymphocytes and macrophages, has been found to be expressed in the mucosa of the gastrointestinal tract and is a potent chemoattractant for various leukocytes. AIM To examine CCL4 expression and its genetic polymorphism rs10491121 in patients with colorectal cancer (CRC) and evaluate their prognostic significance. METHODS Luminex technology was used to determine CCL4 Levels in CRC tissue (n = 98), compared with paired normal tissue, and in plasma from patients with CRC (n = 103), compared with healthy controls (n = 97). Included patients had undergone surgical resection for primary colorectal adenocarcinomas between 1996 and 2019 at the Department of Surgery, Ryhov County Hospital, Jönköping, Sweden. Reverse transcription quantitative PCR was used to investigate the CCL4 gene expression in CRC tissue (n = 101). Paired normal tissue and TaqMan single nucleotide polymorphism assays were used for the CCL4 rs10491121 polymorphism in 610 CRC patients and 409 healthy controls. RESULTS The CCL4 protein and messenger RNA expression levels were higher in CRC tissue than in normal paired tissue (90%, P < 0.001 and 45%, P < 0.05, respectively). CRC tissue from patients with localized disease had 2.8-fold higher protein expression levels than that from patients with disseminated disease. Low CCL4 protein expression levels in CRC tissue were associated with a 30% lower cancer-specific survival rate in patients (P < 0.01). The level of plasma CCL4 was 11% higher in CRC patients than in healthy controls (P < 0.05) and was positively correlated (r = 0.56, P < 0.01) with the CCL4 protein level in CRC tissue. The analysis of CCL4 gene polymorphism rs10491121 showed a difference (P < 0.05) between localized disease and disseminated disease in the right colon, with a dominance of allele A in localized disease. Moreover, the

Gastrointestinal stromal tumor management is extremely challenging, particularly the metastatic disease. The underlying mechanism in metastasis spread remains largely unknown. We aimed to characterize miRNAs involved in the metastatic process in gastrointestinal stromal tumor. Material & methods: Eight primary tumors and 18 synchronous metastases were analyzed through miRNA Taqman arrays or assays. Results: miRNAs profiles revealed similar expression in primary site and metastases. Pair-wise correlation coefficient between primary tumor and metastases was significant for each patient (p < 0.0001 for all profiled patients). Conclusion: Our study, the largest including primary tumors and metastases so far performed, highlighted perpetuation of miRNAs features in metastatic lesions and that the primary origin appears to be the main determinant of the metastases miRNA profile.

Background The aim of this study is to evaluate the relationship between the aspartate aminotransaminase (AST) and alanine aminotransaminase (ALT) ratio and local disease control in patients with head and neck squamous cell carcinomas (HNSCC) treated with radiotherapy/chemoradiotherapy. Methods We calculated the pre-treatment AST/ALT ratio in 670 patients with HNSCC treated with radiotherapy (n = 309, 46.1%) or chemoradiotherapy (n = 361, 53.9%). Results Five-year local recurrence-free survival for patients with a low AST/ALT ratio value (n = 529, 79.0%) was 75.0% (95% CI: 71.1-78.9), and for patients with a high value (n = 141, 21.0%) it was 53.4% (CI 95: 44.4-62.4) (p = 0.0001). In a multivariable analysis, patients with a high ratio had nearly twice the risk of having a local tumor recurrence (HR 1.97, 95% CI 1.42-2.75, p = 0.0001). Conclusion The AST/ALT ratio was independently associated with the risk of local recurrence in patients with HNSCC treated with radiotherapy or chemoradiotherapy.

Despite overall improvements in cancer survival due to earlier diagnosis and better treatment, socio-economically disadvantaged people have lower cancer survival than more advantaged people. We aimed to examine differences in cancer survival by area-level socio-economic disadvantage in Victoria, Australia and assess whether these inequalities varied by year of diagnosis, age at diagnosis, time since diagnosis and sex. Cases diagnosed with a first primary cancer in 2001-2015 were identified using the Victorian Cancer Registry and followed to the end of 2016. Five-year net survival and the excess risk of death due to a cancer diagnosis were estimated. People living in more disadvantaged areas had lower five-year survival than residents of less disadvantaged regions for 21 of 29 cancer types: head and neck, oesophagus, stomach, colorectum, anus/anal canal, liver, gallbladder/ biliary tract, pancreas, lung, melanoma, connective/soft tissue, female breast, ovary, prostate, kidney, bladder, brain and central nervous system, unknown primary, non-Hodgkin lymphoma, multiple myeloma and leukemia. The observed lower survival in more deprived regions persisted over time, except head and neck cancer, for which the gap in survival has widened. Socio-economic inequalities in survival decreased with increasing age at diagnosis for cancers of connective/soft tissue, bladder and unknown primary. For colorectal cancer, the observed survival disadvantage in lower socio-economic regions was greater for men than for women, while for brain and central nervous system tumours, it was larger for women. Cancer survival is generally lower for residents of more socio-economically disadvantaged areas. Identifying the underlying reasons for these inequalities is important and may help to identify effective interventions to increase survival for underprivileged cancer patients.Copyright © 2020 Afshar et al. This is an open access article distributed under the terms of the Creative Commons Attribut

Introduction: There is conflicting evidence regarding whether routine preoperative biliary drainage (PBD) should be performed if clinically warranted prior to a pylorus-preserving pancreaticoduodenectomy (PPP) for resectable pancreatic head cancer. In addition, there are limited studies that investigated whether PBD with metal or plastic biliary stents have differing impacts on PBD-related complication rates, post PPP surgical outcomes, and healthcare resource utilisation. Aims & Methods: An Australian multicentre retrospective cohort study was conducted which included patients who underwent PBD prior to PPP from 2010 to 2019. Patients included received PBD based on one or more of: cholangitis defined by revised Tokyo guidelines, level of total bilirubin >=40 mumol/L, expected time to operation >=7 days, or receiving neoadjuvant chemotherapy. The aim of this study was to compare PBD with fully covered self-expandable metal stent (FCSEMS) compared to plastic stents in terms of the rate of endoscopic reintervention, stent related complication and surgical complications in patients with resectable pancreatic head cancer who later underwent a PPD. Result(s): 106 patients underwent PBD. 32 patients (30.19%) received a FCSEMS versus 74 (69.81%) with plastic). The mean age was 66.75 +/- 9.79 years, 47.17% were male and the baseline bilirubin was 184.91 +/- 113.59 mumol/L. Both FCSEMS and plastic effectively reduced bilirubin (DELTA140.04 +/- 113.04 mumol/L from baseline) with no difference between the FCSEMS arm and the plastic arm (DELTA134.56 +/- 108.35 mumol/L vs DELTA152.19 +/- 123.74 mumol/L, p-value:0.47). There was no difference in the PBD complication rates in the FCSEMS and plastic stent groups respectively: readmission (p-value=0.40), pancreatitis (p-value=0.25), cholangitis (p-value=0.35), haemorrhage (p-value=0.51), stent occlusion without cholangitis (p-value=0.09), and reintervention with either ERCP or PTC (p-value=0.21). There were no cases of stent related

Despite overall improvements in cancer survival due to earlier diagnosis and better treatment, socio-economically disadvantaged people have lower cancer survival than more advantaged people. We aimed to examine differences in cancer survival by area-level socio-economic disadvantage in Victoria, Australia and assess whether these inequalities varied by year of diagnosis, age at diagnosis, time since diagnosis and sex. Cases diagnosed with a first primary cancer in 2001-2015 were identified using the Victorian Cancer Registry and followed to the end of 2016. Five-year net survival and the excess risk of death due to a cancer diagnosis were estimated. People living in more disadvantaged areas had lower five-year survival than residents of less disadvantaged regions for 21 of 29 cancer types: head and neck, oesophagus, stomach, colorectum, anus/anal canal, liver, gallbladder/ biliary tract, pancreas, lung, melanoma, connective/soft tissue, female breast, ovary, prostate, kidney, bladder, brain and central nervous system, unknown primary, non-Hodgkin lymphoma, multiple myeloma and leukemia. The observed lower survival in more deprived regions persisted over time, except head and neck cancer, for which the gap in survival has widened. Socio-economic inequalities in survival decreased with increasing age at diagnosis for cancers of connective/soft tissue, bladder and unknown primary. For colorectal cancer, the observed survival disadvantage in lower socio-economic regions was greater for men than for women, while for brain and central nervous system tumours, it was larger for women. Cancer survival is generally lower for residents of more socio-economically disadvantaged areas. Identifying the underlying reasons for these inequalities is important and may help to identify effective interventions to increase survival for underprivileged cancer patients.Copyright © 2020 Afshar et al. This is an open access article distributed under the terms of the Creative Commons Attribut

Introduction: There is conflicting evidence regarding whether routine preoperative biliary drainage (PBD) should be performed if clinically warranted prior to a pylorus-preserving pancreaticoduodenectomy (PPP) for resectable pancreatic head cancer. In addition, there are limited studies that investigated whether PBD with metal or plastic biliary stents have differing impacts on PBD-related complication rates, post PPP surgical outcomes, and healthcare resource utilisation. Aims & Methods: An Australian multicentre retrospective cohort study was conducted which included patients who underwent PBD prior to PPP from 2010 to 2019. Patients included received PBD based on one or more of: cholangitis defined by revised Tokyo guidelines, level of total bilirubin >=40 mumol/L, expected time to operation >=7 days, or receiving neoadjuvant chemotherapy. The aim of this study was to compare PBD with fully covered self-expandable metal stent (FCSEMS) compared to plastic stents in terms of the rate of endoscopic reintervention, stent related complication and surgical complications in patients with resectable pancreatic head cancer who later underwent a PPD. Result(s): 106 patients underwent PBD. 32 patients (30.19%) received a FCSEMS versus 74 (69.81%) with plastic). The mean age was 66.75 +/- 9.79 years, 47.17% were male and the baseline bilirubin was 184.91 +/- 113.59 mumol/L. Both FCSEMS and plastic effectively reduced bilirubin (DELTA140.04 +/- 113.04 mumol/L from baseline) with no difference between the FCSEMS arm and the plastic arm (DELTA134.56 +/- 108.35 mumol/L vs DELTA152.19 +/- 123.74 mumol/L, p-value:0.47). There was no difference in the PBD complication rates in the FCSEMS and plastic stent groups respectively: readmission (p-value=0.40), pancreatitis (p-value=0.25), cholangitis (p-value=0.35), haemorrhage (p-value=0.51), stent occlusion without cholangitis (p-value=0.09), and reintervention with either ERCP or PTC (p-value=0.21). There were no cases of stent related

Background and Aim: The role of preoperative biliary drainage (PBD) before a pylorus-preserving pancreaticoduodenectomy (PPPD) for resectable pancreatic or periampullary malignancy remains unclear. When PBD is clinically warranted, there is limited evidence to guide the choice of fully covered self-expandable metal stents (FCSEMS) or plastic stents in terms of PBD-related complication rates, post-PPPD surgical outcomes, and health care resource utilization. The aim of this study was to compare the efficacy and safety of endoscopic PBD before PPPD with FCSEMS compared with plastic stents in terms of the rate of preoperative, operative, and postoperative adverse events. Our secondary outcome measures included duration of surgery, length of hospitalization, intensive care unit stay, and overall health care resource utilization up to 120 days after PBD. Method(s): We conducted a Victorian multicenter retrospective cohort study that included adult patients who underwent endoscopic PBD before PPPD for one or more of the following indications: cholangitis defined by revised Tokyo guidelines, level of total bilirubin >= 40 mumol/L, expected time to PPPD >= 7 days, or neoadjuvant chemotherapy. Patients were deemed resectable by pancreatic protocol computed tomography or magnetic resonance imaging reviewed at a multidisciplinary discussion. Result(s): A total of 106 patients underwent PBD before PPPD at five Victorian tertiary hospitals from 2010 to 2019. Of these, 32 patients (30.19%) received FCSEMS versus 74 (69.81%) with plastic stents. The mean age was 66.75 +/- 9.79 years, 47.17% of patients were male, and the baseline bilirubin level was 184.91 +/- 113.59 mumol/L. Both FCSEMS and plastic stents effectively reduced bilirubin levels (DELTA140.04 +/- 113.04 mumol/L from baseline), with no difference between the FCSEMS arm and the plastic stents arm (DELTA134.56 +/- 108.35 mumol/L vs DELTA152.19 +/- 123.74 mumol/L; P = 0.47). There was no difference in PBD complication rat

Background: While adjuvant therapy provides a survival benefit for patients (pts) with early-stage pancreatic cancer there are currently no biomarkers that define pts that are more or less likely to benefit from such treatment. This prospective study investigated the use of circulating tumour DNA (ctDNA) as a marker of residual disease, where detection could predict recurrence. Method(s): Patients newly diagnosed with operable pancreatic adenocarcinoma were enrolled. PCR-based-SafeSeqS assays were used to identify mutations at codons 12, 13 and 61 of KRAS in the primary tumor and to detect ctDNA in plasma samples. Patient management was as per standard of care, blinded to ctDNA data. Result(s): From January 2015 to June 2017, 42 pts with matched plasma samples, collected pre- and post-operatively, and tumor tissue available were evaluated. The median time between surgery and post-op blood collection was 6.3 (range:4-8) weeks. RAS mutations were identified in 38 (90.5%) tumor samples. ctDNA was detected in 23/37 (62.2%) pre-op and 13/35 (37.1%) post-op plasma samples. In multivariate analysis including stage, and resection margin, ctDNA status was the only statistically significant variable. Pre-op ctDNA detection was associated with worse median recurrence free survival (RFS), 10.3 months versus not reached, (Hazard Ratio (HR),3.4; 95% confidence interval (CI), 1.5- 7.6; P = 0.005) and 5.4 months versus 17.1 months, (HR, 5.4; 95% CI, 4.7-37.3; P < 0.0001) post-operatively. Similarly, the presence of ctDNA was associated with worse median overall survival (OS), 13.8 months versus not reached pre-operatively, (HR,3.4; 95% CI 1.1 to 8.3; P = 0.04) and 10.6 months versus not reached (HR,4.5; 95% CI 2.4-28.6; P = 0.001) post-operatively. Notably, recurrence occurred in 13 of 13 pts with detectable post-op ctDNA, despite more than half receiving standard adjuvant chemotherapy. Conclusion(s): ctDNA analysis is a promising prognostic marker in early-stage pancreatic cancer

Intramedullary spinal cord metastasis (ISCM) is rare and occurs most commonly in the setting of advanced malignancy. The optimal management pathways are not well defined and treatment outcomes from contemporary therapies remain variable. We report a case of a 49-year-old woman with known primary papillary thyroid carcinoma, who presented with rapidly progressive clinical features of Brown-Sequard syndrome. A detailed pooled analysis of the literature was conducted to characterise the clinical and demographic features, management options, and expected survival outcomes for cases of ISCM. We secondarily performed a subgroup analysis on the incidence, clinical and management characteristics of thyroid carcinoma ISCM.Copyright © 2017 Elsevier Ltd

Introduction and Objectives: PSMA PET/ CT has demonstrated superior sensitivity in detecting prostate cancer metastases compared to traditional staging modalities and seen a high degree of utilisation in the Australian setting. However, there is little data published on the role of PSMA PET/CT in detecting and diagnosing primary prostate cancer. We compared the accuracy of PSMA PET/CT to multiparametric MRI for (Table presented) the detection of clinically significant primary prostate cancer. Method(s): A local prospective database (REDCap-Monash) was maintained on patients who underwent MRI in our group urology practice from July 2013 to December 2017. All patients who had an MRI for diagnosis of prostate cancer, subsequent transperineal biopsy, and a PSMA PET/CT for initial staging were included, with significant cancer being defined as greater than or equal to Gleason 3 + 4 = 7 (ISUP Grade Group 2). Result(s): The database contained 2283 patients who underwent prostate MRI. 239 patients subsequently underwent both biopsy and PSMA PET/CT. 202 biopsies (84.5%) showed significant cancer. Of the non-significant cancer cases, 21 (8.8%) revealed Grade Group 1 lesions and 16 (6.7%) were benign. For significant cancers, 189 PSMA PET/CT scans demonstrated local PSMA avidity in the prostate, compared to 174 positive (PIRADS 4 or 5) MRI scans. MRI detected fewer insignificant cancers, but resulted in more false negatives. Overall, sensitivity and specificity for PSMA PET/CT and MRI respectively were 93.6%, 64.9% and 87.1%, 70.3%. Conclusion(s): In this highly-selected cohort of patients undergoing prostate MRI, transperineal biopsy and PSMA PET/CT for staging as part of clinical practice, PSMA PET/CT outperformed MRI in detecting clinically significant primary prostate cancer. It is proposed that PSMA PET may be used in both diagnosis of primary cancers and staging, although costeffectiveness in this dual role warrants further investigation. Higher sensitivity achieved by P

Background: Comprehensive cancer risk management guidelines for individuals at high multi-organ cancer risk are lacking. Research studies support whole body MRI as part of a baseline surveillance assessment. Aim(s): To estimate the prevalence and incidence of investigable lesions in a high-risk population and investigate mutational signatures in peripheral blood as an early detection mechanism; and to assess the acceptability, psychosocial impact and cost effectiveness of the surveillance program. Method(s): The surveillance program includes annual whole-body MRI, physical examination, full blood evaluation, fecal occult blood testing, breast MRI and 2-5 yearly colonoscopy/endoscopy. Deep sequencing will be used to detect genetic signatures of malignancy in cell free plasma. Psychometric evaluations are undertaken and participants complete cost diaries. Medicare/PBS data is also utilized. Result(s): Since July 2013, 42 TP53 pathogenic variant carriers (25F, 17M; age 18-63 years) have been enrolled. After completion of 38 first-year whole body MRI scans, three new asymptomatic malignancies (lumbar liposarcoma, Gleason score 8 and 9 prostate cancers) have been detected. Second- and third-year whole body MRI scans (45 total) detected an additional four new primary cancers; thymic pleomorphic liposarcoma, pelvic chondrosarcoma, renal leiomyosarcoma and a pheochromocytoma. All other screening procedures have been normal. Mutational signatures of malignancy in the peripheral blood were detectable by sequencing. Preliminary psychosocial data indicate no lasting adverse effects. Conclusion(s): Evaluation of the surveillance schedule is ongoing. Detection of seven asymptomatic primary malignancies (treated with curative intent), in conjunction with the acceptability and lack of negative psychological impact supports evaluation over a longer term.

Purpose: To evaluate the use of single-fraction palliative radiation therapy (SFRT) for the management of bone metastases (BM) in Victoria, Australia. Methods and Materials: This is a population-based cohort of patients with cancer who received radiation therapy for BM between 2012 and 2017 as captured in the Victorian Radiotherapy Minimum Data Set. The primary outcome was proportion of SFRT use. The Cochrane-Armitage test for trend was used to evaluate changes in practice over time. Multivariable logistic regression was used to assess factors associated with SFRT use. Result(s): Of the 18,158 courses of radiation therapy for BM delivered to a total of 10,956 patients, 17% were SFRT. There was no significant change in SFRT use over time, from 18% in 2012 to 19% in 2017 (P = .07). SFRT was less commonly given to the skull (4%) and spine (14%), compared with the shoulder (37%) and ribs (53%). Patients with lung cancer (21%) were most likely to receive SFRT, followed by those with prostate cancers (18%) and gastrointestinal cancers (16%). Patients from regional/remote areas were more likely to have SFRT compared with those in major cities (22% vs 16%, P < .001). Patients treated in public institutions were more likely to have SFRT compared with those treated in private institutions (22% vs 10%, P < .001). In multivariable analyses, increasing age, lung cancer, higher socioeconomic status, residence in regional/ remote areas, and being treated in public institutions were factors independently associated with increased likelihood of receiving SFRT. Conclusion(s): SFRT appears underused for BM in Australia over time, with variation in practice by patient, tumor, sociodemographic, geographical, and institutional provider factors.Copyright © 2019 Elsevier Inc.

Purpose: To evaluate the adoption of the Royal Australian and New Zealand College of Radiologists Choosing Wisely (CW) radiation oncology recommendations before and after the release of the recommendations. Methods and Materials: The Victorian Radiotherapy Minimum Data Set captures details of radiation therapy delivered in the state of Victoria, Australia. This study included the following 3 groups of patients relevant to 3 of the 5 CW recommendations: women who received a diagnosis of early-stage breast cancer at age >=50 years who had breast radiation therapy (excluding nodal irradiation), patients with cancer who had palliative bone radiation therapy (excluding those with primary bone malignancies), and patients with cancer who had stereotactic radiation therapy to the brain (excluding those with primary malignancies of the central nervous system). The outcomes of interest were use of hypofractionated breast radiation therapy (<25 fractions), use of long-course palliative bone radiation therapy (>10 fractions), and use of adjuvant whole brain radiation therapy within 1 month of stereotactic radiation therapy. The Cochrane-Armitage test was used to evaluate changes in practice over time. Result(s): Among the 8204 patients who had breast radiation therapy, there was an increase in hypofractionation use from 42% in 2013 to 82% in 2017 (P <.001). The progressive increase in hypofractionation use was observed across institutions. Of the 15,634 courses of palliative bone radiation therapy delivered, only 1279 (8%) were >10 fractions, and this decreased from 10% in 2013 to 5% in 2017 (P <.001). Of the 1049 patients who received stereotactic radiation therapy for brain metastases, only 2% had adjuvant whole brain radiation therapy, and this decreased from 4% in 2013 to 0.7% in 2017 (P =.02). Conclusion(s): There was a significant change in radiation oncology practice in Australia between 2013 and 2017, in line with the CW recommendations. However, some of the recommendat

Background and Aim: The role of preoperative biliary drainage (PBD) before a pylorus-preserving pancreaticoduodenectomy (PPPD) for resectable pancreatic or periampullary malignancy remains unclear. When PBD is clinically warranted, there is limited evidence to guide the choice of fully covered self-expandable metal stents (FCSEMS) or plastic stents in terms of PBD-related complication rates, post-PPPD surgical outcomes, and health care resource utilization. The aim of this study was to compare the efficacy and safety of endoscopic PBD before PPPD with FCSEMS compared with plastic stents in terms of the rate of preoperative, operative, and postoperative adverse events. Our secondary outcome measures included duration of surgery, length of hospitalization, intensive care unit stay, and overall health care resource utilization up to 120 days after PBD. Method(s): We conducted a Victorian multicenter retrospective cohort study that included adult patients who underwent endoscopic PBD before PPPD for one or more of the following indications: cholangitis defined by revised Tokyo guidelines, level of total bilirubin >= 40 mumol/L, expected time to PPPD >= 7 days, or neoadjuvant chemotherapy. Patients were deemed resectable by pancreatic protocol computed tomography or magnetic resonance imaging reviewed at a multidisciplinary discussion. Result(s): A total of 106 patients underwent PBD before PPPD at five Victorian tertiary hospitals from 2010 to 2019. Of these, 32 patients (30.19%) received FCSEMS versus 74 (69.81%) with plastic stents. The mean age was 66.75 +/- 9.79 years, 47.17% of patients were male, and the baseline bilirubin level was 184.91 +/- 113.59 mumol/L. Both FCSEMS and plastic stents effectively reduced bilirubin levels (DELTA140.04 +/- 113.04 mumol/L from baseline), with no difference between the FCSEMS arm and the plastic stents arm (DELTA134.56 +/- 108.35 mumol/L vs DELTA152.19 +/- 123.74 mumol/L; P = 0.47). There was no difference in PBD complication rat

Background: While adjuvant therapy provides a survival benefit for patients (pts) with early-stage pancreatic cancer there are currently no biomarkers that define pts that are more or less likely to benefit from such treatment. This prospective study investigated the use of circulating tumour DNA (ctDNA) as a marker of residual disease, where detection could predict recurrence. Method(s): Patients newly diagnosed with operable pancreatic adenocarcinoma were enrolled. PCR-based-SafeSeqS assays were used to identify mutations at codons 12, 13 and 61 of KRAS in the primary tumor and to detect ctDNA in plasma samples. Patient management was as per standard of care, blinded to ctDNA data. Result(s): From January 2015 to June 2017, 42 pts with matched plasma samples, collected pre- and post-operatively, and tumor tissue available were evaluated. The median time between surgery and post-op blood collection was 6.3 (range:4-8) weeks. RAS mutations were identified in 38 (90.5%) tumor samples. ctDNA was detected in 23/37 (62.2%) pre-op and 13/35 (37.1%) post-op plasma samples. In multivariate analysis including stage, and resection margin, ctDNA status was the only statistically significant variable. Pre-op ctDNA detection was associated with worse median recurrence free survival (RFS), 10.3 months versus not reached, (Hazard Ratio (HR),3.4; 95% confidence interval (CI), 1.5- 7.6; P = 0.005) and 5.4 months versus 17.1 months, (HR, 5.4; 95% CI, 4.7-37.3; P < 0.0001) post-operatively. Similarly, the presence of ctDNA was associated with worse median overall survival (OS), 13.8 months versus not reached pre-operatively, (HR,3.4; 95% CI 1.1 to 8.3; P = 0.04) and 10.6 months versus not reached (HR,4.5; 95% CI 2.4-28.6; P = 0.001) post-operatively. Notably, recurrence occurred in 13 of 13 pts with detectable post-op ctDNA, despite more than half receiving standard adjuvant chemotherapy. Conclusion(s): ctDNA analysis is a promising prognostic marker in early-stage pancreatic cancer

Intramedullary spinal cord metastasis (ISCM) is rare and occurs most commonly in the setting of advanced malignancy. The optimal management pathways are not well defined and treatment outcomes from contemporary therapies remain variable. We report a case of a 49-year-old woman with known primary papillary thyroid carcinoma, who presented with rapidly progressive clinical features of Brown-Sequard syndrome. A detailed pooled analysis of the literature was conducted to characterise the clinical and demographic features, management options, and expected survival outcomes for cases of ISCM. We secondarily performed a subgroup analysis on the incidence, clinical and management characteristics of thyroid carcinoma ISCM.Copyright © 2017 Elsevier Ltd

Introduction and Objectives: PSMA PET/ CT has demonstrated superior sensitivity in detecting prostate cancer metastases compared to traditional staging modalities and seen a high degree of utilisation in the Australian setting. However, there is little data published on the role of PSMA PET/CT in detecting and diagnosing primary prostate cancer. We compared the accuracy of PSMA PET/CT to multiparametric MRI for (Table presented) the detection of clinically significant primary prostate cancer. Method(s): A local prospective database (REDCap-Monash) was maintained on patients who underwent MRI in our group urology practice from July 2013 to December 2017. All patients who had an MRI for diagnosis of prostate cancer, subsequent transperineal biopsy, and a PSMA PET/CT for initial staging were included, with significant cancer being defined as greater than or equal to Gleason 3 + 4 = 7 (ISUP Grade Group 2). Result(s): The database contained 2283 patients who underwent prostate MRI. 239 patients subsequently underwent both biopsy and PSMA PET/CT. 202 biopsies (84.5%) showed significant cancer. Of the non-significant cancer cases, 21 (8.8%) revealed Grade Group 1 lesions and 16 (6.7%) were benign. For significant cancers, 189 PSMA PET/CT scans demonstrated local PSMA avidity in the prostate, compared to 174 positive (PIRADS 4 or 5) MRI scans. MRI detected fewer insignificant cancers, but resulted in more false negatives. Overall, sensitivity and specificity for PSMA PET/CT and MRI respectively were 93.6%, 64.9% and 87.1%, 70.3%. Conclusion(s): In this highly-selected cohort of patients undergoing prostate MRI, transperineal biopsy and PSMA PET/CT for staging as part of clinical practice, PSMA PET/CT outperformed MRI in detecting clinically significant primary prostate cancer. It is proposed that PSMA PET may be used in both diagnosis of primary cancers and staging, although costeffectiveness in this dual role warrants further investigation. Higher sensitivity achieved by P

Background: Comprehensive cancer risk management guidelines for individuals at high multi-organ cancer risk are lacking. Research studies support whole body MRI as part of a baseline surveillance assessment. Aim(s): To estimate the prevalence and incidence of investigable lesions in a high-risk population and investigate mutational signatures in peripheral blood as an early detection mechanism; and to assess the acceptability, psychosocial impact and cost effectiveness of the surveillance program. Method(s): The surveillance program includes annual whole-body MRI, physical examination, full blood evaluation, fecal occult blood testing, breast MRI and 2-5 yearly colonoscopy/endoscopy. Deep sequencing will be used to detect genetic signatures of malignancy in cell free plasma. Psychometric evaluations are undertaken and participants complete cost diaries. Medicare/PBS data is also utilized. Result(s): Since July 2013, 42 TP53 pathogenic variant carriers (25F, 17M; age 18-63 years) have been enrolled. After completion of 38 first-year whole body MRI scans, three new asymptomatic malignancies (lumbar liposarcoma, Gleason score 8 and 9 prostate cancers) have been detected. Second- and third-year whole body MRI scans (45 total) detected an additional four new primary cancers; thymic pleomorphic liposarcoma, pelvic chondrosarcoma, renal leiomyosarcoma and a pheochromocytoma. All other screening procedures have been normal. Mutational signatures of malignancy in the peripheral blood were detectable by sequencing. Preliminary psychosocial data indicate no lasting adverse effects. Conclusion(s): Evaluation of the surveillance schedule is ongoing. Detection of seven asymptomatic primary malignancies (treated with curative intent), in conjunction with the acceptability and lack of negative psychological impact supports evaluation over a longer term.

Purpose: To evaluate the use of single-fraction palliative radiation therapy (SFRT) for the management of bone metastases (BM) in Victoria, Australia. Methods and Materials: This is a population-based cohort of patients with cancer who received radiation therapy for BM between 2012 and 2017 as captured in the Victorian Radiotherapy Minimum Data Set. The primary outcome was proportion of SFRT use. The Cochrane-Armitage test for trend was used to evaluate changes in practice over time. Multivariable logistic regression was used to assess factors associated with SFRT use. Result(s): Of the 18,158 courses of radiation therapy for BM delivered to a total of 10,956 patients, 17% were SFRT. There was no significant change in SFRT use over time, from 18% in 2012 to 19% in 2017 (P = .07). SFRT was less commonly given to the skull (4%) and spine (14%), compared with the shoulder (37%) and ribs (53%). Patients with lung cancer (21%) were most likely to receive SFRT, followed by those with prostate cancers (18%) and gastrointestinal cancers (16%). Patients from regional/remote areas were more likely to have SFRT compared with those in major cities (22% vs 16%, P < .001). Patients treated in public institutions were more likely to have SFRT compared with those treated in private institutions (22% vs 10%, P < .001). In multivariable analyses, increasing age, lung cancer, higher socioeconomic status, residence in regional/ remote areas, and being treated in public institutions were factors independently associated with increased likelihood of receiving SFRT. Conclusion(s): SFRT appears underused for BM in Australia over time, with variation in practice by patient, tumor, sociodemographic, geographical, and institutional provider factors.Copyright © 2019 Elsevier Inc.

Purpose: To evaluate the adoption of the Royal Australian and New Zealand College of Radiologists Choosing Wisely (CW) radiation oncology recommendations before and after the release of the recommendations. Methods and Materials: The Victorian Radiotherapy Minimum Data Set captures details of radiation therapy delivered in the state of Victoria, Australia. This study included the following 3 groups of patients relevant to 3 of the 5 CW recommendations: women who received a diagnosis of early-stage breast cancer at age >=50 years who had breast radiation therapy (excluding nodal irradiation), patients with cancer who had palliative bone radiation therapy (excluding those with primary bone malignancies), and patients with cancer who had stereotactic radiation therapy to the brain (excluding those with primary malignancies of the central nervous system). The outcomes of interest were use of hypofractionated breast radiation therapy (<25 fractions), use of long-course palliative bone radiation therapy (>10 fractions), and use of adjuvant whole brain radiation therapy within 1 month of stereotactic radiation therapy. The Cochrane-Armitage test was used to evaluate changes in practice over time. Result(s): Among the 8204 patients who had breast radiation therapy, there was an increase in hypofractionation use from 42% in 2013 to 82% in 2017 (P <.001). The progressive increase in hypofractionation use was observed across institutions. Of the 15,634 courses of palliative bone radiation therapy delivered, only 1279 (8%) were >10 fractions, and this decreased from 10% in 2013 to 5% in 2017 (P <.001). Of the 1049 patients who received stereotactic radiation therapy for brain metastases, only 2% had adjuvant whole brain radiation therapy, and this decreased from 4% in 2013 to 0.7% in 2017 (P =.02). Conclusion(s): There was a significant change in radiation oncology practice in Australia between 2013 and 2017, in line with the CW recommendations. However, some of the recommendat

Introduction: Synchronous oligometastatic (sOM) disease is an oncological concept characterized by a limited cancer burden. Patients with oligometastasis could potentially benefit from local radical treatments. Despite the fact that the sOM condition is well recognized, a universal definition, including a specific definition for NSCLC, is not yet available. The aim of this systematic review was to summarize the definitions of and staging requirements for use of the term synchronous oligometastatic in the context of NSCLC.Methods: The key issue was formulated in one research question according to the population, intervention, comparator, and outcomes strategy. The question was introduced in MEDLINE (OvidSP). All articles dealing with sOM NSCLC and providing a definition of synchronous oligometastasis in NSCLC were selected and analyzed.Results: A total of 21 eligible articles focusing on sOM NSCLC were retrieved and analyzed. In 17 studies (81%), patients had to be staged with magnetic resonance imaging or computed tomography of the brain, thoracic and abdominal computed tomography, and positron emission tomography. The total number of metastases allowed in the definitions ranged from one to eight, but in 38.1% of studies the maximum number was 5. Most of the publications did not define the number of involved organs or the maximum number of metastases per organ. For mediastinal lymph node involvement, only five articles (27.8%) counted this as a metastatic site.Conclusions: No uniform definition of sOM NSCLC could be retrieved by this systematic review. However, extended staging was mandated in most of the studies. An accepted oncological definition of synchronous oligometastasis is essential for patient selection to define prospective clinical trials. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Introduction: Synchronous oligometastatic (sOM) disease is an oncological concept characterized by a limited cancer burden. Patients with oligometastasis could potentially benefit from local radical treatments. Despite the fact that the sOM condition is well recognized, a universal definition, including a specific definition for NSCLC, is not yet available. The aim of this systematic review was to summarize the definitions of and staging requirements for use of the term synchronous oligometastatic in the context of NSCLC.Methods: The key issue was formulated in one research question according to the population, intervention, comparator, and outcomes strategy. The question was introduced in MEDLINE (OvidSP). All articles dealing with sOM NSCLC and providing a definition of synchronous oligometastasis in NSCLC were selected and analyzed.Results: A total of 21 eligible articles focusing on sOM NSCLC were retrieved and analyzed. In 17 studies (81%), patients had to be staged with magnetic resonance imaging or computed tomography of the brain, thoracic and abdominal computed tomography, and positron emission tomography. The total number of metastases allowed in the definitions ranged from one to eight, but in 38.1% of studies the maximum number was 5. Most of the publications did not define the number of involved organs or the maximum number of metastases per organ. For mediastinal lymph node involvement, only five articles (27.8%) counted this as a metastatic site.Conclusions: No uniform definition of sOM NSCLC could be retrieved by this systematic review. However, extended staging was mandated in most of the studies. An accepted oncological definition of synchronous oligometastasis is essential for patient selection to define prospective clinical trials. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Epithelial-to-mesenchymal transition (EMT) has been proposed to be important for metastatic dissemination. However, recent studies have challenged the requirement of EMT for metastasis. Here, we assessed in different models of primary skin squamous cell carcinomas (SCCs) whether EMT is associated with metastasis. The incidence of metastasis was much higher in SCCs presenting EMT compared to SCCs without EMT, supporting the notion that a certain degree of EMT is required to initiate the metastatic cascade in primary skin SCCs. Most circulating tumor cells presented EMT, whereas most lung metastasis did not present EMT, showing that mesenchymal-to-epithelial transition is important for metastatic colonization. In contrast, immunodeficient mice transplanted with SCCs, whether displaying EMT or not, presented metastasis. Altogether, our data demonstrate that the association of EMT and metastasis is model dependent, and metastasis of primary skin SCCs is associated with EMT., SCOPUS: ar.j, info:eu-repo/semantics/published

Background: Bevacizumab (BEV) with fluoropyrimidine-containing chemotherapy is well-established for patients (pts) with mCRC. There is a need for reproducible, validated, inexpensive and accessible prognostic markers to aid in treatment selection. Pretreatment levels of systemic inflammatory markers including the neutrophil to lymphocyte ratio (NLR) have been shown retrospectively to be prognostic in many tumors. This study aimed to prospectively evaluate the relationship between NLR and treatment outcomes in previously untreated mCRC pts receiving BEV-based therapy. Method(s): ASCENT (NCT01588990) is an openlabel, single arm, phase-IV, multi-center study. Pts received 1st-line BEV+XELOX or mFOLFOX6 in phase A (PhA) with planned continuation of BEV+FOLFIRI beyond 1st progression in phase B (PhB). Primary analysis: association of NLR with progression free survival (PFS). Secondary analyses: overall survival (OS) and safety. Sub-study: safety in pts with intact primary in situ (PIS) and resected primary tumor (RPT). Result(s): 128 pts started PhA; median age 63.5 years (range: 26-84), 70(55%) females, 51(40%) PIS, 71(56%) and 56(44%) were PS 0 and >= 1; respectively. 53(41%) pts entered PhB. The median baseline (b) NLR was 3.2 (range: 1.5- 20.4) with 32(25%) pts having a baseline level > 5. The hazard ratio (HR) for PFS by NLR > 5 vs <=5 was 1.4 (95% CI: 0.9-2.2; p = 1.01). Median PFS was 9.2 months (mo; 95% CI: 7.9-10.8) for PhA and 6.7 mo (95% CI: 3.0-8.2) for PhB. HR for OS based on baseline NLR > 5 vs <=5 was 1.6 (95% CI: 1.0-2.7; p = 0.052). Based on a multivariate model, the 12-month predicted OS probability for pts with PS 0, no metastatic liver disease and <= 3 sites of other metastatic disease, was 87% in pts with bNLR <= 5 and 79% in pts with bNLR > 5. Median OS was 25 mo (95% CI: 19.2-29.7) for the full analysis set and 14.9 mo for PhB. Treatment related toxicities were numerically and qualitatively consistent with prior experience. There were 4(3%) instanc

Purpose: The pituitary gland is an unusual site for metastatic spread, but as patients with metastatic malignancy are living longer, it may become more prevalent. Compression of important anatomy adjacent to the sella may produce disabling symptoms and endocrine derangement, leading to significant morbidity. Method(s): An ambispective review of patient records between 2013 and 2017 from three neurosurgical centres was performed. After identifying cases, further investigation was performed to evaluate patient demographic, symptoms at presentation, radiological and histological findings, management, and outcome. Result(s): Our investigation identified 12 patients with pituitary metastasis. The average age of the cases was 63.4 years, with breast (n = 4) and lung (n = 4) being the most common primary cancers. In half the cases there was a history of metastatic disease, while in one-quarter of cases, pituitary symptoms were the first sign of malignancy. Adenohypophyseal dysfunction (83%), diabetes insipidus (DI) (75%), headache (67%) and visual field defects (67%) were the most common findings at presentation. Glucocorticoid replacement increased the sensitivity for diagnosis of DI. All cases were contrast enhancing on MRI and the endoscopic trans-sphenoidal approach was preferred for biopsy and debulking. Conclusion(s): The pituitary should not be overlooked as a site of metastasis and sellar symptoms may be the first presentation of neoplastic disease. Any biochemical or clinical sign of pituitary pathology in a patient with known cancer should raise suspicion for sellar metastasis. Moreover, the development of DI or ophthalmoplegia from any pituitary lesion is suggestive of metastatic disease even in patients with no known primary.Copyright © 2018, Springer Science+Business Media, LLC, part of Springer Nature.

Introduction & Objective: PSMA PET/ CT demonstrates superior sensitivity in staging prostate cancer compared to traditional modalities and seen a high degree of utilisation in Australia1. However, there is little data published on the role of PSMA PET/CT in diagnosing primary prostate cancer. We compared the accuracy of PSMA PET/CT to multiparametric MRI for detecting clinically significant primary prostate cancer. Method(s): A local prospective database (REDCap-Monash) was maintained on patients who underwent MRI in our group urology practice from July-2013 to December- 2017. All patients who underwent MRI, subsequent transperineal biopsy, and PSMA PET/CT for initial staging were included, with significant cancer defined as greater than or equal to ISUP Grade Group 2. Result(s): 2,283 patients underwent prostate MRI. 239 patients subsequently underwent biopsy and PSMA PET/CT. 202 biopsies (84.5%) showed significant cancer. Of the non-significant cancers, 21 (8.8%) revealed Grade Group 1 lesions and 16 (6.7%) were benign. For significant cancers, 189 PSMA PET/CT scans demonstrated local prostate PSMA avidity, compared to 174 positive (PIRADS 4/5) MRI scans. MRI detected fewer insignificant cancers, but more false- negatives. Overall, sensitivity and specificity for PSMA PET/CT and MRI respectively were 93.6%, 18.9% and 86.1%, 70.3% (p < 0.05). Conclusion(s): In this highly-selected cohort of patients, PSMA PET/CT outperformed MRI in detecting clinically significant primary prostate cancer. This can enhance its uses, in detecting and staging primary cancers, although cost-effectiveness in this dual-role warrants further investigation. Higher sensitivity achieved by PET/CT comes at the expense of detecting clinically insignificant disease, evidenced by higher false-positive rates. Furthermore, soft-tissue resolution is inferior to MRI.

Background: Vertebral compression fractures (VCFs) are a common complication of osteoporosis and spinal neoplasms. Vertebroplasty presents a treatment option for VCFs that cause pain and disability. Predicting pain relief outcomes based on pre-treatment factors may robustly identify patients likely to benefit from the procedure, and guide clinical decision-making. Machine learning (ML) offers the ability to analyse large volumes of clinical data to formulate accurate outcome predictions. Purpose(s): The aim of this study was to assess the feasibility of ML techniques to develop a model for accurate prediction of pain relief outcomes after vertebroplasty. Method(s): This was a retrospective study of a prospectively collected multicentre database. All available demographic and procedural factors were integrated into ML models as predictors, including demographic data, VCF aetiology, number and location, procedural details and visual analogue scale (VAS) scores pre-and post-procedure. Successful clinical outcome was defined as a reduction by at least 67% (two-thirds) in VAS pain scores. ML algorithms were trained on these data to develop a model capable of categorising predictors into good and poor outcomes. Result(s): We analysed 5,785 patients with 20,463 VCFs treated by vertebroplasty. The majority (75%, n = 4,312) were female with a median age of 73.5 (range 19-100) years. The most common VCF aetiology was primary osteoporosis (55.2%), followed by secondary osteoporosis (14.7%), metastatic disease (13.2%), primary malignancy (5.5%), trauma (6.4%) and other (5.2%). Most patients had two levels treated (23.9%) followed by one (19.2%) and three levels (17.5%). The majority also had pre*procedure MRI (89.4%). Vertebroplasty was highly effective in pain relief with 97.9% (n = 5,662) reporting clinically significant reduction in VAS. ML analysis based on a naive Bayes model (Figure 1) demonstrated that the number of treated levels, primary malignancy as aetiology, pre-pr

Objective: Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has demonstrated superior sensitivity in detecting prostate cancer metastases compared to traditional staging modalities and seen a high degree of utilisation in the Australian setting.1 However, there is little data published on the role of PSMA PET/CT in diagnosing primary prostate cancer. We compared the accuracy of PSMA PET/CT to multi-parametric MRI for the detection of clinically significant primary prostate cancer. Method(s): A local prospective database (REDCap-Monash) was maintained on patients who underwent MRI in our group urology practice from July 2013 to December 2017. All patients who had an MRI for diagnosis of prostate cancer, subsequent transperineal biopsy and a PSMA PET/CT for initial staging were included, with significant cancer being defined as greater than or equal to Gleason 3+4=7 (ISUP Grade Group 2). Result(s): The database contained 2283 patients who underwent prostate MRI. Two-hundred thirty-nine patients subsequently underwent both biopsy and PSMA PET/CT. Two hundred biopsies (84.5%) showed significant cancer. Of the non-significant cancer cases, 21 (8.8%) revealed Grade Group 1 lesions and 16 (6.7%) were benign. For significant cancers, 189 PSMA PET/CT scans demonstrated local PSMA avidity in the prostate, compared to 174 positive (PIRADS 4 or 5) MRI scans. MRI detected fewer insignificant cancers, but resulted in more false negatives. Overall, sensitivity and specificity for PSMA PET/CT and MRI, respectively, were 93.6%, 18.9% and 86.1%, 70.3% (P < 0.05). Conclusion(s): In this highly selected cohort of patients undergoing prostate MRI, transperineal biopsy and PSMA PET/CT as part of clinical practice, PSMA PET/CT outperformed MRI in detecting clinically significant primary prostate cancer. This can enhance its uses, in detecting and staging primary cancers, although cost-effectiveness in this dual role warrants further inves

Introduction: Paediatric and adolescent breast pathologic disorders are relatively rare and present differently to adults. A 10-year review of a major children's hospital service was conducted. The objectives were to Describe the spectrum of pathology Review reports for terminology (e.g. Tanner classification and gynaecomastia). Method(s): A 10-year retrospective assessment of breast ultrasound examinations in patients aged 0-16 was performed. The results were classified by pathology and the need for follow-up imaging. They were also considered for the use of consistent terminology. Result(s): Ultrasound of the paediatric breast is a very uncommon examination in this public hospital setting (0.001%). While the normal breast is the most common finding, a broad range of pathologies was encountered. Primary malignancy is exceedingly rare. (Zero cases). Inconsistent use of terminology and understanding of normal anatomy can result in unnecessary uncertainty in final reports. Conclusion(s): Normal findings are the common outcome for patients. Standardised terminology and targeted reported may improve patient treatment/outcome. Take home message: Understanding the Tanner stages of the paediatric breast can assist in distinguishing normal appearances from pathology in this age group.

BACKGROUND: The optimal treatment strategy for older rectal cancer patients remains unclear. The current study aimed to compare treatment and survival of rectal cancer patients aged 80+. METHODS: Patients of >= 80 years diagnosed with rectal cancer between 2001 and 2010 were included. Population-based cohorts from Belgium (BE), Denmark (DK), the Netherlands (NL), Norway (NO) and Sweden (SE) were compared side by side for neighbouring countries on treatment strategy and 5-year relative survival (RS), adjusted for sex and age. Analyses were performed separately for stage I-III patients and stage IV patients. RESULTS: Overall, 19 634 rectal cancer patients were included. For stage I-III patients, 5-year RS varied from 61.7% in BE to 72.3% in SE. Proportion of preoperative radiotherapy ranged between 7.9% in NO and 28.9% in SE. For stage IV patients, 5-year RS differed from 2.8% in NL to 5.6% in BE. Rate of patients undergoing surgery varied from 22.2% in DK to 40.8% in NO. CONCLUSIONS: Substantial variation was observed in the 5-year relative survival between European countries for rectal cancer patients aged 80+, next to a wide variation in treatment, especially in the use of preoperative radiotherapy in stage I-III patients and in the rate of patients undergoing surgery in stage IV patients.

Purpose: The pituitary gland is an unusual site for metastatic spread, but as patients with metastatic malignancy are living longer, it may become more prevalent. Compression of important anatomy adjacent to the sella may produce disabling symptoms and endocrine derangement, leading to significant morbidity. Method(s): An ambispective review of patient records between 2013 and 2017 from three neurosurgical centres was performed. After identifying cases, further investigation was performed to evaluate patient demographic, symptoms at presentation, radiological and histological findings, management, and outcome. Result(s): Our investigation identified 12 patients with pituitary metastasis. The average age of the cases was 63.4 years, with breast (n = 4) and lung (n = 4) being the most common primary cancers. In half the cases there was a history of metastatic disease, while in one-quarter of cases, pituitary symptoms were the first sign of malignancy. Adenohypophyseal dysfunction (83%), diabetes insipidus (DI) (75%), headache (67%) and visual field defects (67%) were the most common findings at presentation. Glucocorticoid replacement increased the sensitivity for diagnosis of DI. All cases were contrast enhancing on MRI and the endoscopic trans-sphenoidal approach was preferred for biopsy and debulking. Conclusion(s): The pituitary should not be overlooked as a site of metastasis and sellar symptoms may be the first presentation of neoplastic disease. Any biochemical or clinical sign of pituitary pathology in a patient with known cancer should raise suspicion for sellar metastasis. Moreover, the development of DI or ophthalmoplegia from any pituitary lesion is suggestive of metastatic disease even in patients with no known primary.Copyright © 2018, Springer Science+Business Media, LLC, part of Springer Nature.

Background: Bevacizumab (BEV) with fluoropyrimidine-containing chemotherapy is well-established for patients (pts) with mCRC. There is a need for reproducible, validated, inexpensive and accessible prognostic markers to aid in treatment selection. Pretreatment levels of systemic inflammatory markers including the neutrophil to lymphocyte ratio (NLR) have been shown retrospectively to be prognostic in many tumors. This study aimed to prospectively evaluate the relationship between NLR and treatment outcomes in previously untreated mCRC pts receiving BEV-based therapy. Method(s): ASCENT (NCT01588990) is an openlabel, single arm, phase-IV, multi-center study. Pts received 1st-line BEV+XELOX or mFOLFOX6 in phase A (PhA) with planned continuation of BEV+FOLFIRI beyond 1st progression in phase B (PhB). Primary analysis: association of NLR with progression free survival (PFS). Secondary analyses: overall survival (OS) and safety. Sub-study: safety in pts with intact primary in situ (PIS) and resected primary tumor (RPT). Result(s): 128 pts started PhA; median age 63.5 years (range: 26-84), 70(55%) females, 51(40%) PIS, 71(56%) and 56(44%) were PS 0 and >= 1; respectively. 53(41%) pts entered PhB. The median baseline (b) NLR was 3.2 (range: 1.5- 20.4) with 32(25%) pts having a baseline level > 5. The hazard ratio (HR) for PFS by NLR > 5 vs <=5 was 1.4 (95% CI: 0.9-2.2; p = 1.01). Median PFS was 9.2 months (mo; 95% CI: 7.9-10.8) for PhA and 6.7 mo (95% CI: 3.0-8.2) for PhB. HR for OS based on baseline NLR > 5 vs <=5 was 1.6 (95% CI: 1.0-2.7; p = 0.052). Based on a multivariate model, the 12-month predicted OS probability for pts with PS 0, no metastatic liver disease and <= 3 sites of other metastatic disease, was 87% in pts with bNLR <= 5 and 79% in pts with bNLR > 5. Median OS was 25 mo (95% CI: 19.2-29.7) for the full analysis set and 14.9 mo for PhB. Treatment related toxicities were numerically and qualitatively consistent with prior experience. There were 4(3%) instanc

Introduction & Objective: PSMA PET/ CT demonstrates superior sensitivity in staging prostate cancer compared to traditional modalities and seen a high degree of utilisation in Australia1. However, there is little data published on the role of PSMA PET/CT in diagnosing primary prostate cancer. We compared the accuracy of PSMA PET/CT to multiparametric MRI for detecting clinically significant primary prostate cancer. Method(s): A local prospective database (REDCap-Monash) was maintained on patients who underwent MRI in our group urology practice from July-2013 to December- 2017. All patients who underwent MRI, subsequent transperineal biopsy, and PSMA PET/CT for initial staging were included, with significant cancer defined as greater than or equal to ISUP Grade Group 2. Result(s): 2,283 patients underwent prostate MRI. 239 patients subsequently underwent biopsy and PSMA PET/CT. 202 biopsies (84.5%) showed significant cancer. Of the non-significant cancers, 21 (8.8%) revealed Grade Group 1 lesions and 16 (6.7%) were benign. For significant cancers, 189 PSMA PET/CT scans demonstrated local prostate PSMA avidity, compared to 174 positive (PIRADS 4/5) MRI scans. MRI detected fewer insignificant cancers, but more false- negatives. Overall, sensitivity and specificity for PSMA PET/CT and MRI respectively were 93.6%, 18.9% and 86.1%, 70.3% (p < 0.05). Conclusion(s): In this highly-selected cohort of patients, PSMA PET/CT outperformed MRI in detecting clinically significant primary prostate cancer. This can enhance its uses, in detecting and staging primary cancers, although cost-effectiveness in this dual-role warrants further investigation. Higher sensitivity achieved by PET/CT comes at the expense of detecting clinically insignificant disease, evidenced by higher false-positive rates. Furthermore, soft-tissue resolution is inferior to MRI.

Background: Vertebral compression fractures (VCFs) are a common complication of osteoporosis and spinal neoplasms. Vertebroplasty presents a treatment option for VCFs that cause pain and disability. Predicting pain relief outcomes based on pre-treatment factors may robustly identify patients likely to benefit from the procedure, and guide clinical decision-making. Machine learning (ML) offers the ability to analyse large volumes of clinical data to formulate accurate outcome predictions. Purpose(s): The aim of this study was to assess the feasibility of ML techniques to develop a model for accurate prediction of pain relief outcomes after vertebroplasty. Method(s): This was a retrospective study of a prospectively collected multicentre database. All available demographic and procedural factors were integrated into ML models as predictors, including demographic data, VCF aetiology, number and location, procedural details and visual analogue scale (VAS) scores pre-and post-procedure. Successful clinical outcome was defined as a reduction by at least 67% (two-thirds) in VAS pain scores. ML algorithms were trained on these data to develop a model capable of categorising predictors into good and poor outcomes. Result(s): We analysed 5,785 patients with 20,463 VCFs treated by vertebroplasty. The majority (75%, n = 4,312) were female with a median age of 73.5 (range 19-100) years. The most common VCF aetiology was primary osteoporosis (55.2%), followed by secondary osteoporosis (14.7%), metastatic disease (13.2%), primary malignancy (5.5%), trauma (6.4%) and other (5.2%). Most patients had two levels treated (23.9%) followed by one (19.2%) and three levels (17.5%). The majority also had pre*procedure MRI (89.4%). Vertebroplasty was highly effective in pain relief with 97.9% (n = 5,662) reporting clinically significant reduction in VAS. ML analysis based on a naive Bayes model (Figure 1) demonstrated that the number of treated levels, primary malignancy as aetiology, pre-pr

Objective: Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has demonstrated superior sensitivity in detecting prostate cancer metastases compared to traditional staging modalities and seen a high degree of utilisation in the Australian setting.1 However, there is little data published on the role of PSMA PET/CT in diagnosing primary prostate cancer. We compared the accuracy of PSMA PET/CT to multi-parametric MRI for the detection of clinically significant primary prostate cancer. Method(s): A local prospective database (REDCap-Monash) was maintained on patients who underwent MRI in our group urology practice from July 2013 to December 2017. All patients who had an MRI for diagnosis of prostate cancer, subsequent transperineal biopsy and a PSMA PET/CT for initial staging were included, with significant cancer being defined as greater than or equal to Gleason 3+4=7 (ISUP Grade Group 2). Result(s): The database contained 2283 patients who underwent prostate MRI. Two-hundred thirty-nine patients subsequently underwent both biopsy and PSMA PET/CT. Two hundred biopsies (84.5%) showed significant cancer. Of the non-significant cancer cases, 21 (8.8%) revealed Grade Group 1 lesions and 16 (6.7%) were benign. For significant cancers, 189 PSMA PET/CT scans demonstrated local PSMA avidity in the prostate, compared to 174 positive (PIRADS 4 or 5) MRI scans. MRI detected fewer insignificant cancers, but resulted in more false negatives. Overall, sensitivity and specificity for PSMA PET/CT and MRI, respectively, were 93.6%, 18.9% and 86.1%, 70.3% (P < 0.05). Conclusion(s): In this highly selected cohort of patients undergoing prostate MRI, transperineal biopsy and PSMA PET/CT as part of clinical practice, PSMA PET/CT outperformed MRI in detecting clinically significant primary prostate cancer. This can enhance its uses, in detecting and staging primary cancers, although cost-effectiveness in this dual role warrants further inves

Introduction: Paediatric and adolescent breast pathologic disorders are relatively rare and present differently to adults. A 10-year review of a major children's hospital service was conducted. The objectives were to Describe the spectrum of pathology Review reports for terminology (e.g. Tanner classification and gynaecomastia). Method(s): A 10-year retrospective assessment of breast ultrasound examinations in patients aged 0-16 was performed. The results were classified by pathology and the need for follow-up imaging. They were also considered for the use of consistent terminology. Result(s): Ultrasound of the paediatric breast is a very uncommon examination in this public hospital setting (0.001%). While the normal breast is the most common finding, a broad range of pathologies was encountered. Primary malignancy is exceedingly rare. (Zero cases). Inconsistent use of terminology and understanding of normal anatomy can result in unnecessary uncertainty in final reports. Conclusion(s): Normal findings are the common outcome for patients. Standardised terminology and targeted reported may improve patient treatment/outcome. Take home message: Understanding the Tanner stages of the paediatric breast can assist in distinguishing normal appearances from pathology in this age group.

In this thesis, we used support vector machines (SVMs) to build a tissue-of-origin classifier of 17 cancer types. Our classifier, which uses RNA expression data from over 20000 genes, works with high accuracy on primary (97.6%), metastasis (91.9%) and cell-line samples (71.1%). With the goal of enabling cheaper diagnostics for the clinics, we performed feature selection through recursive feature elimination (RFE) and identified a gene signature of just 120 genes that maintains almost all of the predictive power. We explored how our model could achieve such great accuracy and found that it recognises characteristics from healthy tissues rather than cancer. In order to help disseminate our results among clinicians and basic researchers, we released our trained model and its code in the command-line tool TOPOS (Tissue-of-Origin Predictor of OncoSamples). To our knowledge, this is the first time that a metastasis classifier is developed based on RNAseq data, and we hope to pave the way for others to do the same in the future. (I would like to explain that the reason why I cannot upload the thesis to UPCommons is that we are waiting for peer review to publish a paper with the results. Once the paper has been published, I would be happy to upload it to UPCommons as well if the paper's guidelines allow us to do so.)

BACKGROUND: The optimal treatment strategy for older rectal cancer patients remains unclear. The current study aimed to compare treatment and survival of rectal cancer patients aged 80+. METHODS: Patients of >= 80 years diagnosed with rectal cancer between 2001 and 2010 were included. Population-based cohorts from Belgium (BE), Denmark (DK), the Netherlands (NL), Norway (NO) and Sweden (SE) were compared side by side for neighbouring countries on treatment strategy and 5-year relative survival (RS), adjusted for sex and age. Analyses were performed separately for stage I-III patients and stage IV patients. RESULTS: Overall, 19 634 rectal cancer patients were included. For stage I-III patients, 5-year RS varied from 61.7% in BE to 72.3% in SE. Proportion of preoperative radiotherapy ranged between 7.9% in NO and 28.9% in SE. For stage IV patients, 5-year RS differed from 2.8% in NL to 5.6% in BE. Rate of patients undergoing surgery varied from 22.2% in DK to 40.8% in NO. CONCLUSIONS: Substantial variation was observed in the 5-year relative survival between European countries for rectal cancer patients aged 80+, next to a wide variation in treatment, especially in the use of preoperative radiotherapy in stage I-III patients and in the rate of patients undergoing surgery in stage IV patients.

IMPORTANCE Standard treatment for endometrial cancer involves removal of the uterus, tubes, ovaries, and lymph nodes. Few randomized trials have compared disease-free survival outcomes for surgical approaches. OBJECTIVE To investigate whether total laparoscopic hysterectomy (TLH) is equivalent to total abdominal hysterectomy (TAH) in women with treatment-naive endometrial cancer. DESIGN, SETTING, AND PARTICIPANTS The Laparoscopic Approach to Cancer of the Endometrium (LACE) trialwas a multinational, randomized equivalence trial conducted between October 7, 2005, and June 30, 2010, in which 27 surgeons from 20 tertiary gynecological cancer centers in Australia,New Zealand, and Hong Kong randomized 760 women with stage I endometrioid endometrial cancer to either TLH or TAH. Follow-up ended on March 3, 2016. INTERVENTIONS Patientswere randomly assigned to undergo TAH (n = 353) or TLH (n = 407). MAIN OUTCOMES AND MEASURES The primary outcomewas disease-free survival, which was measured as the interval between surgery and the date of first recurrence, including disease progression or the development of a new primary cancer or death assessed at 4.5 years after randomization. The prespecified equivalence margin was 7%or less. Secondary outcomes included recurrence of endometrial cancer and overall survival. RESULTS Patients were followed up for a median of 4.5 years. Of 760 patients who were randomized (mean age, 63 years), 679 (89%) completed the trial. At 4.5 years of follow-up, disease-free survival was 81.3%in the TAH group and 81.6%in the TLH group. The disease-free survival rate difference was 0.3%(favoring TLH; 95%CI, -5.5%to 6.1%; P = .007), meeting criteria for equivalence. There was no statistically significant between-group difference in recurrence of endometrial cancer (28/353 in TAH group [7.9%] vs 33/407 in TLH group [8.1%]; risk difference, 0.2%[95%CI, -3.7%to 4.0%]; P = .93) or in overall survival (24/353 in TAH group [6.8%] vs 30/407 in TLH group [7.4%]; r

Background: Neuroendocrine tumours (NETs) are uncommon. Little data exist to guide follow-up in resected disease, with no consensus regarding the optimal follow-up frequency or modality. Follow-up imaging regimens are extrapolated from other gastrointestinal tumours. As NETs are heterogeneous, this may result in both over-use and underuse of investigations in patients. Method(s): A population-based retrospective cohort study using linked data from the Institute for Clinical Evaluative Sciences and the Ontario Cancer Registry (capturing more than 99% of incident cases in Ontario) was conducted to evaluate patients diagnosed with gastroenteropancreatic NETs in Ontario, Canada from 1994 to 2012. Recurrence-free survival and the frequency of cross sectional imaging (abdominal computed tomography (aCT), magnetic resonance imaging (aMRI) and ultrasound (aUS)) were the main outcomes. Result(s): Nine hundred and thirty-six patients were identified with median follow-up 47 months. The mean age was 59, 51% were female, and distribution of primary cancers was: small intestine 47%, pancreas 20%, large intestine 21%, rectum 6.4%, stomach 6.0%. The median survival time to a composite outcome of recurrence or death was 7.2 years, and 9.5 years if censoring on death. The cumulative incidence of recurrence was 8.4% (95% CI 6.8%to 10.3%) within one year, 33.7% (95% CI 30.4% to 36.9%) within five years, and 48.5% (95% CI 44.4% to 52.4%) within 10 years. The rate of recurrence significantly increased with age (HR=1.529 for age 50-70 compared to<50, p=0.0003) and pancreatic primary (HR=1.463, p=0.0006), but not income quintile (p=0.1071), rurality (p=0.1931) or gender (p=0.3787). The rate of use of aCTs, aMRIs and aUS decreased over time, from 1.04 per 100 patient-days in months 1-3 to 0.22 at months 49-60. On average, 1.59 abdominal CTs per patient were performed in the first year, 0.83 in the second year and 0.52 in years 3-5. Conclusion(s): Unlike colon cancer, significant numbers of

Introduction and Objectives: To assess whether PSMA PET CT changes preoperative management in the Uro-oncology multidisciplinary meeting (MDM) at Monash Health and to determine the concordance between conventional cancer staging (CT and/or bone scan) and PSMA PET CT. Method(s): All pre-operative prostate cancer patients discussed at the Monash Health MDM who underwent PSMA PET CT scanning over a 16 month period were included in this retrospective study. Patient demographics, Gleason scores, PSA, staging information and PSMA PET CT results were analyzed using t-test and ranksum test. Correlation between conventional staging modalities was compared against PSMA PET CT using Cohen's Kappa. Result(s): 29 patients met the inclusion criteria. Median PSA was higher in patients with positive extra-prostatic PSMA PET CT lesions 35.4 (13-76) than negative 13 (1.8-53) p = 0.005. 14 patients had Gleason 7 disease and 15 patients had Gleason >=8 disease. All patients had PSMA PET CT avid primary cancer. 26% (6/23) of cases with negative conventional staging were found to have extra-prostatic disease on PSMA PET CT. All 6 cases had their management plan changed as a result. 33% (2/6) of cases with positive conventional staging found no PSMA PET CT evidence of extra-prostatic disease, of which one case had their management plan changed. Imaging non-concordance was greatest in Gleason 7 cancers- 40% of conventional staging negative patients had PSMA PET CT positive extra-prostatic avid disease. Conclusion(s): PSMA PET CT has resulted in a paradigm shift at Monash Health in the treatment of prostate cancer. All patients with staging positive extra-prostatic pre-operative PSMA PET CT are now treated with radiotherapy. PSMA PET CT is a promising new imaging technique in the pre-operative staging of prostate cancer. It is a useful tool in aiding decision making for treatment. Further research is warranted to better assess its efficacy and implementation.

IMPORTANCE Standard treatment for endometrial cancer involves removal of the uterus, tubes, ovaries, and lymph nodes. Few randomized trials have compared disease-free survival outcomes for surgical approaches. OBJECTIVE To investigate whether total laparoscopic hysterectomy (TLH) is equivalent to total abdominal hysterectomy (TAH) in women with treatment-naive endometrial cancer. DESIGN, SETTING, AND PARTICIPANTS The Laparoscopic Approach to Cancer of the Endometrium (LACE) trialwas a multinational, randomized equivalence trial conducted between October 7, 2005, and June 30, 2010, in which 27 surgeons from 20 tertiary gynecological cancer centers in Australia,New Zealand, and Hong Kong randomized 760 women with stage I endometrioid endometrial cancer to either TLH or TAH. Follow-up ended on March 3, 2016. INTERVENTIONS Patientswere randomly assigned to undergo TAH (n = 353) or TLH (n = 407). MAIN OUTCOMES AND MEASURES The primary outcomewas disease-free survival, which was measured as the interval between surgery and the date of first recurrence, including disease progression or the development of a new primary cancer or death assessed at 4.5 years after randomization. The prespecified equivalence margin was 7%or less. Secondary outcomes included recurrence of endometrial cancer and overall survival. RESULTS Patients were followed up for a median of 4.5 years. Of 760 patients who were randomized (mean age, 63 years), 679 (89%) completed the trial. At 4.5 years of follow-up, disease-free survival was 81.3%in the TAH group and 81.6%in the TLH group. The disease-free survival rate difference was 0.3%(favoring TLH; 95%CI, -5.5%to 6.1%; P = .007), meeting criteria for equivalence. There was no statistically significant between-group difference in recurrence of endometrial cancer (28/353 in TAH group [7.9%] vs 33/407 in TLH group [8.1%]; risk difference, 0.2%[95%CI, -3.7%to 4.0%]; P = .93) or in overall survival (24/353 in TAH group [6.8%] vs 30/407 in TLH group [7.4%]; r

Background: Neuroendocrine tumours (NETs) are uncommon. Little data exist to guide follow-up in resected disease, with no consensus regarding the optimal follow-up frequency or modality. Follow-up imaging regimens are extrapolated from other gastrointestinal tumours. As NETs are heterogeneous, this may result in both over-use and underuse of investigations in patients. Method(s): A population-based retrospective cohort study using linked data from the Institute for Clinical Evaluative Sciences and the Ontario Cancer Registry (capturing more than 99% of incident cases in Ontario) was conducted to evaluate patients diagnosed with gastroenteropancreatic NETs in Ontario, Canada from 1994 to 2012. Recurrence-free survival and the frequency of cross sectional imaging (abdominal computed tomography (aCT), magnetic resonance imaging (aMRI) and ultrasound (aUS)) were the main outcomes. Result(s): Nine hundred and thirty-six patients were identified with median follow-up 47 months. The mean age was 59, 51% were female, and distribution of primary cancers was: small intestine 47%, pancreas 20%, large intestine 21%, rectum 6.4%, stomach 6.0%. The median survival time to a composite outcome of recurrence or death was 7.2 years, and 9.5 years if censoring on death. The cumulative incidence of recurrence was 8.4% (95% CI 6.8%to 10.3%) within one year, 33.7% (95% CI 30.4% to 36.9%) within five years, and 48.5% (95% CI 44.4% to 52.4%) within 10 years. The rate of recurrence significantly increased with age (HR=1.529 for age 50-70 compared to<50, p=0.0003) and pancreatic primary (HR=1.463, p=0.0006), but not income quintile (p=0.1071), rurality (p=0.1931) or gender (p=0.3787). The rate of use of aCTs, aMRIs and aUS decreased over time, from 1.04 per 100 patient-days in months 1-3 to 0.22 at months 49-60. On average, 1.59 abdominal CTs per patient were performed in the first year, 0.83 in the second year and 0.52 in years 3-5. Conclusion(s): Unlike colon cancer, significant numbers of

Patient-derived xenograft (PDX) mouse models of cancer are emerging as an important component of personalized precision cancer therapy. However, most models currently offered to patients have their tumors subcutaneously-transplanted in immunodeficient mice, which rarely metastasize. In contrast, orthotopic-transplant patient-derived models, termed patient-derived orthotopic xenografts (PDOX), usually metastasize as in the patient. We demonstrate in the present report why orthotopic models are so important for the patient, since primary and metastatic tumors developed in an orthotopic model can have differential chemosensitivity, not detectable in standard subcutaneous tumor models. A subcutaneous nude mouse model of HER-2 expressing cervical carcinoma was not sensitive to entinostat (a benzamide histone deactylase inhibitor), which also did not inhibit primary tumor growth in a PDOX model of the same tumor. However, in the PDOX model, entinostat alone significantly reduced the metastatic tumor burden, compared to the control. Thus, only the PDOX model could be used to discover the anti-metastatic activity of entinostat for this patient. The results of the present report indicate the importance of using mouse models that can recapitulate metastatic cancer for precisely individualizing cancer therapy.