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Background: Identifying people at risk of poor outcomes following treatment for substance use disorders is important for developing tailored services. The aim of this study was to test whether a brief measure of internalizing and externalizing behavior could identify young adults at high risk of psychiatric care episodes and criminal offending up to four years after enrolment in treatment for substance use disorder. Methods: Clients aged 15–25 years from a randomized multicenter study were included (N = 457). At baseline, all completed the YouthMap12 screener, a measure of internalizing symptoms (IP6) and externalizing problems (EP6). We used accelerated failure time regression to assess time to psychiatric care and criminal offending, adjusting for baseline occurrence, gender, age, treatment group, and uptake area. Youden's J was used to assess optimal cut-points for risk of events. Results: The IP6 was associated with shorter time to psychiatric care following treatment enrolment (beta = −0.71, 95% confidence interval [CI] = −0.94 to −0.48; adjusted beta = −0.45, 95% CI = −0.66 to −0.25). The EP6 was associated with shorter time to criminal offending, coefficient = −0.32, 95% CI = −0.44 to −0.19; adjusted coefficient = −0.18, 95% CI = −0.30 to −0.06). Optimal cut-points were two or more for the IP6 and three or more for the EP6. Conclusions: The IP6 and the EP6, two simple and easily administered instruments, can identify young adults who are at an increased risk of future criminal offending or in need of psychiatric care. The findings lend support to using the 12-item YouthMap, as it identifies relevant risks, is compatible with local service delivery needs, and is theoretically and empirically supported. © 2022 The Author(s)

Background: Identifying people at risk of poor outcomes following treatment for substance use disorders is important for developing tailored services. The aim of this study was to test whether a brief measure of internalizing and externalizing behavior could identify young adults at high risk of psychiatric care episodes and criminal offending up to four years after enrolment in treatment for substance use disorder. Methods: Clients aged 15–25 years from a randomized multicenter study were included (N = 457). At baseline, all completed the YouthMap12 screener, a measure of internalizing symptoms (IP6) and externalizing problems (EP6). We used accelerated failure time regression to assess time to psychiatric care and criminal offending, adjusting for baseline occurrence, gender, age, treatment group, and uptake area. Youden's J was used to assess optimal cut-points for risk of events. Results: The IP6 was associated with shorter time to psychiatric care following treatment enrolment (beta = −0.71, 95% confidence interval [CI] = −0.94 to −0.48; adjusted beta = −0.45, 95% CI = −0.66 to −0.25). The EP6 was associated with shorter time to criminal offending, coefficient = −0.32, 95% CI = −0.44 to −0.19; adjusted coefficient = −0.18, 95% CI = −0.30 to −0.06). Optimal cut-points were two or more for the IP6 and three or more for the EP6. Conclusions: The IP6 and the EP6, two simple and easily administered instruments, can identify young adults who are at an increased risk of future criminal offending or in need of psychiatric care. The findings lend support to using the 12-item YouthMap, as it identifies relevant risks, is compatible with local service delivery needs, and is theoretically and empirically supported. © 2022 The Author(s)

BackgroundSevere muscle stiffness (SMS) in dogs with hypercortisolism (HC) is uncommon.ObjectivesTo evaluate signalment, presentation, treatments, and long-term outcomes of dogs with concurrent HC and SMS.AnimalsThirty-seven dogs.MethodsMedical records of dogs with HC and concurrent SMS were recruited from 10 institutions. Clinical information, test results, therapeutic responses, and survival times were reviewed.ResultsAll 37 dogs with HC and SMS had pituitary-dependent hypercortisolism (PDH); 36/37 weighed <20 kg. Signs and test results were typical of PDH aside from SMS, initially diagnosed in all 4 limbs in 9, pelvic limbs of 22, and thoracic limbs of 6 dogs. Hypercortisolism and SMS were diagnosed together in 3 dogs; HC 1-36 months before SMS in 23; SMS 1-12 months before HC in 11. Mitotane or trilostane, given to control HC in 36/37 dogs, improved or resolved HC signs in 28; SMS did not resolve, remaining static or worsening in 31/36 dogs, mildly improving in 5/19 dogs given additional therapies. Progression of SMS included additional limbs in 10 dogs and the masticatory muscles of 2. The median survival time from diagnosis of SMS was 965 days (range, 8-1188).Conclusions and clinical importanceConcurrent SMS and HC is uncommon, possibly affecting only dogs with PDH. Development of SMS might occur before or after diagnosis of HC. Apart from SMS, the clinical picture and survival time of these dogs seem indistinguishable from those of dogs with HC in general. However, while muscle weakness usually resolves with HC treatment SMS does not.

Background: Identifying people at risk of poor outcomes following treatment for substance use disorders is important for developing tailored services. The aim of this study was to test whether a brief measure of internalizing and externalizing behavior could identify young adults at high risk of psychiatric care episodes and criminal offending up to four years after enrolment in treatment for substance use disorder. Methods: Clients aged 15–25 years from a randomized multicenter study were included (N = 457). At baseline, all completed the YouthMap12 screener, a measure of internalizing symptoms (IP6) and externalizing problems (EP6). We used accelerated failure time regression to assess time to psychiatric care and criminal offending, adjusting for baseline occurrence, gender, age, treatment group, and uptake area. Youden's J was used to assess optimal cut-points for risk of events. Results: The IP6 was associated with shorter time to psychiatric care following treatment enrolment (beta = −0.71, 95% confidence interval [CI] = −0.94 to −0.48; adjusted beta = −0.45, 95% CI = −0.66 to −0.25). The EP6 was associated with shorter time to criminal offending, coefficient = −0.32, 95% CI = −0.44 to −0.19; adjusted coefficient = −0.18, 95% CI = −0.30 to −0.06). Optimal cut-points were two or more for the IP6 and three or more for the EP6. Conclusions: The IP6 and the EP6, two simple and easily administered instruments, can identify young adults who are at an increased risk of future criminal offending or in need of psychiatric care. The findings lend support to using the 12-item YouthMap, as it identifies relevant risks, is compatible with local service delivery needs, and is theoretically and empirically supported. © 2022 The Author(s)

Introduction: Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease with great heterogeneity. Biological prognostic markers are needed for the patients to plan future supportive treatment, palliative treatment, and end-of-life decisions. In addition, prognostic markers are greatly needed for the randomization in clinical trials. Objective: This study aimed to test the ALS Functional Rating Scale-Revised (ALSFRS-R) progression rate (ΔFS) as a prognostic marker of survival in a Danish ALS cohort. Methods: The ALSFRS-R score at test date in association with duration of symptoms, from the onset of symptoms until test date, (defined as ΔFS’) was calculated for 90 Danish patients diagnosed with either probable or definite sporadic ALS. Median survival time was then estimated from the onset of symptoms until primary endpoint (either death or tracheostomy). ΔFS’ was subjected to survival analysis using Cox proportional hazards modelling, log-rank test, and Kaplan-Meier survival analysis. Results and conclusions: Both ΔFS’ and age was found to be strong predictors of survival of the Danish ALS cohort. Both variables are easily obtained at the time of diagnosis and could be used by clinicians and ALS patients to plan future supportive and palliative treatment. Furthermore, ΔFS’, is a simple, prognostic marker that predicts survival in the early phase of disease as well as at later stages of the disease.

Aims: Background: Upper gastrointestinal (UGI) cancers (pancreatic, oesophageal and stomach) have a dismal prognosis, with five-year survival of only 7.7-28.5% even when detected in their early stages and treated with a complete resection. UGI cancers are characterised by a high symptom burden. It is critical that patients with these cancers receive the best possible symptomatic control, while the search continues for treatments to improve survival. Recent research has shown that patient-reported outcomes (PROs), integrated into clinical practice in a meaningful way to drive action, are associated with improved patient health outcomes and decrease burden to the healthcare system. Aim(s): To determine whether the systematic measurement, identification and management of PROs in clinical practice, coupled with information support to patients, improves health outcomes for patients with UGI cancers. Methods and Design: A registry-based randomised, multicentre, controlled trial will be designed to assess whether, compared to usual practice, the UGI Cancer Care Coordination (UGICCC) intervention is effective in improving health-related quality of life in patients diagnosed with UGI cancers, as the primary outcome. The UGICCC intervention involves: (1) collection of PROs to allow patients to track and report their symptoms over time; (2) provision of real-time feedback to patients for management of symptoms; and (3) alerts to a care-coordinator of patients reporting severe or worsening symptoms to allow for triage and follow-up as well as provision of real-time reports to clinicians. The secondary outcome measures are to assess whether patients assigned to the intervention arm demonstrate: reduced health service use and emergency department visits; lower level of information needs; timely referral to palliative care services; and increased median survival. These will be evaluated at baseline, 3-, 6- and 12-months. Participants will be recruited from eight hospitals in Victo

Primary CNS lymphoma (PCNSL) in immunocompetent patients is a disease of older adults who are often unsuitable for the high dose therapy or experience substantial morbidity from whole brain radiotherapy. As therapeutic studies in older patients are limited, there is a need for real world data to guide patient care. Here we report a series of 38 consecutive immunocompetent patients with PCNSL treated with curative intent using R-MPV/Ara-C with omission of consolidative radiotherapy in older patients. Outcomes for patients aged < 60 years and > 60 years were similar with overall response rates of 100% vs 85%, (p =.30), 4-year PFS of 81% vs 82% (p =.92) and 4-year OS of 80% vs 77% (p =.52) respectively. This study supports the premise that older patients with PCNSL can be effectively treated with sequential and response-adapted methotrexate (MTX) dosing without the need for WBRT or autologous stem cell transplantation (ASCT).Copyright © 2020 Informa UK Limited, trading as Taylor & Francis Group.

Background and Aim: Sorafenib and lenvatinib are the two oral multikinase inhibitors currently registered in Australia for the treatment of advanced unresectable hepatocellular carcinoma (HCC). We aimed to evaluate the use of these multikinase inhibitors in this setting and to define overall survival, time to progression of disease, and adverse effects associated with therapy. Method(s): We conducted a retrospective cohort study of 71 patients treated with sorafenib (n = 57) and lenvatinib (n = 14) for advanced HCC at a Melbourne tertiary center from 2015 to 2020. Baseline demographic data, tumor characteristics, dosage, adverse effects, and survival from initiation of treatment were collected from medical chart review. Time to radiological and biochemical progression was also recorded. Result(s): In the sorafenib group, 70.18% of patients were classified as Child-Pugh A and 29.82% were classified as Child-Pugh B. A total of 73.68% of patients experienced any adverse effect, and 24.56% of patients experienced a severe grade 3 adverse effect, requiring cessation of therapy. The average number of days to radiological progression was 218.67 (median, 103; range, 21-996), which excluded three outliers who exhibitedspontaneous tumor regression. The average number of days to death from initiation of therapy was 341.86 (median, 196; range, 18-2061). Univariate analysis showed radiological progression was associated with higher Child-Pugh scores (odds ratio [OR], 2.4; P < 0.02), Model for End-Stage Liver Disease scores (OR, 2.96; P < 0.0045), dose reduction of sorafenib (OR, 2.4; P < 0.02), and presence of any adverse effect to therapy (OR, 2.0; P < 0.05). In the lenvatinib group, 50% of treated patients were classified as Child-Pugh B. A total of 85.70% had an adverse event. A subset of 42.85% of patients experienced severe grade 3 adverse effects. The average length of time to radiological progression was 119.14 days (median, 84; range, 24-346), and the average length of t

Introduction &objectives: Some forms of epidermolysis bullosa (EB), notably severe generalized recessive dystrophic EB (RDEB-SG), are associated with an increased risk of developing mucocutaneous squamous cell carcinomas (SCCs) which behave aggressively and are the major cause of mortality in early to midadulthood. We report our centres' experience of EB-associated SCCs over the last 28 years. Materials &methods: An observational, retrospective, double institution case record review of EB patients diagnosed with SCC between July 1991-June 2019. Result(s): Forty-four EB patients with SCC were identified with a total of 221 primary SCCs. They comprised: 31 (70%) with RDEB-SG, 1 (2.3%) with RDEB-pruriginosa, 1 with RDEBinversa (2.3%), 2 (4.5%) with RDEB-generalised intermediate, 3 (6.8%) with junctional EB generalised intermediate (JEB-GI), 5 (11.4%) with dominant dystrophic EB, and 1 (2.3%) with Kindler syndrome. Diagnosis of first SCC was earlier in the RDEB-SG group (median 29.5 years (range 13-52 years)) compared to other groups collectively (median 47.1 years (range 30-89 years)). Most SCCs occurred in the RDEB-SG group, and the majority had multiple tumours (mean 5.8 (range 1-44)). SCC-associated mortality was high in this group (64.5%), with a median survival after diagnosis of first SCC of 2.4 years (range 0.5-12.6 years). Most SCCs were well-differentiated (53.4%) and located on the extremities. Wide local excision was undertaken for the majority of tumours (86.4%). Metastatic disease occurred in 16 of 31 (51.6%) RDEB-SG patients and 1 with JEB-GI. Treatments for metastatic disease included lymph node dissection (n = 6), radiotherapy (n= 5), chemotherapy (n=3), electrochemotherapy (n= 2), and targeted cancer therapies erlotinib (n=1), cetuximab (n =2) and cemiplimab (n= 1). Treatments were generally welltolerated, however were limited in response with the exception of cemiplimab. Conclusion(s): EB-associated SCCs differ from those in the general population: th

Primary CNS lymphoma (PCNSL) in immunocompetent patients is a disease of older adults who are often unsuitable for the high dose therapy or experience substantial morbidity from whole brain radiotherapy. As therapeutic studies in older patients are limited, there is a need for real world data to guide patient care. Here we report a series of 38 consecutive immunocompetent patients with PCNSL treated with curative intent using R-MPV/Ara-C with omission of consolidative radiotherapy in older patients. Outcomes for patients aged < 60 years and > 60 years were similar with overall response rates of 100% vs 85%, (p =.30), 4-year PFS of 81% vs 82% (p =.92) and 4-year OS of 80% vs 77% (p =.52) respectively. This study supports the premise that older patients with PCNSL can be effectively treated with sequential and response-adapted methotrexate (MTX) dosing without the need for WBRT or autologous stem cell transplantation (ASCT).Copyright © 2020 Informa UK Limited, trading as Taylor & Francis Group.

Aims: Background: Upper gastrointestinal (UGI) cancers (pancreatic, oesophageal and stomach) have a dismal prognosis, with five-year survival of only 7.7-28.5% even when detected in their early stages and treated with a complete resection. UGI cancers are characterised by a high symptom burden. It is critical that patients with these cancers receive the best possible symptomatic control, while the search continues for treatments to improve survival. Recent research has shown that patient-reported outcomes (PROs), integrated into clinical practice in a meaningful way to drive action, are associated with improved patient health outcomes and decrease burden to the healthcare system. Aim(s): To determine whether the systematic measurement, identification and management of PROs in clinical practice, coupled with information support to patients, improves health outcomes for patients with UGI cancers. Methods and Design: A registry-based randomised, multicentre, controlled trial will be designed to assess whether, compared to usual practice, the UGI Cancer Care Coordination (UGICCC) intervention is effective in improving health-related quality of life in patients diagnosed with UGI cancers, as the primary outcome. The UGICCC intervention involves: (1) collection of PROs to allow patients to track and report their symptoms over time; (2) provision of real-time feedback to patients for management of symptoms; and (3) alerts to a care-coordinator of patients reporting severe or worsening symptoms to allow for triage and follow-up as well as provision of real-time reports to clinicians. The secondary outcome measures are to assess whether patients assigned to the intervention arm demonstrate: reduced health service use and emergency department visits; lower level of information needs; timely referral to palliative care services; and increased median survival. These will be evaluated at baseline, 3-, 6- and 12-months. Participants will be recruited from eight hospitals in Victo

Introduction &objectives: Some forms of epidermolysis bullosa (EB), notably severe generalized recessive dystrophic EB (RDEB-SG), are associated with an increased risk of developing mucocutaneous squamous cell carcinomas (SCCs) which behave aggressively and are the major cause of mortality in early to midadulthood. We report our centres' experience of EB-associated SCCs over the last 28 years. Materials &methods: An observational, retrospective, double institution case record review of EB patients diagnosed with SCC between July 1991-June 2019. Result(s): Forty-four EB patients with SCC were identified with a total of 221 primary SCCs. They comprised: 31 (70%) with RDEB-SG, 1 (2.3%) with RDEB-pruriginosa, 1 with RDEBinversa (2.3%), 2 (4.5%) with RDEB-generalised intermediate, 3 (6.8%) with junctional EB generalised intermediate (JEB-GI), 5 (11.4%) with dominant dystrophic EB, and 1 (2.3%) with Kindler syndrome. Diagnosis of first SCC was earlier in the RDEB-SG group (median 29.5 years (range 13-52 years)) compared to other groups collectively (median 47.1 years (range 30-89 years)). Most SCCs occurred in the RDEB-SG group, and the majority had multiple tumours (mean 5.8 (range 1-44)). SCC-associated mortality was high in this group (64.5%), with a median survival after diagnosis of first SCC of 2.4 years (range 0.5-12.6 years). Most SCCs were well-differentiated (53.4%) and located on the extremities. Wide local excision was undertaken for the majority of tumours (86.4%). Metastatic disease occurred in 16 of 31 (51.6%) RDEB-SG patients and 1 with JEB-GI. Treatments for metastatic disease included lymph node dissection (n = 6), radiotherapy (n= 5), chemotherapy (n=3), electrochemotherapy (n= 2), and targeted cancer therapies erlotinib (n=1), cetuximab (n =2) and cemiplimab (n= 1). Treatments were generally welltolerated, however were limited in response with the exception of cemiplimab. Conclusion(s): EB-associated SCCs differ from those in the general population: th

Background and Aim: Sorafenib and lenvatinib are the two oral multikinase inhibitors currently registered in Australia for the treatment of advanced unresectable hepatocellular carcinoma (HCC). We aimed to evaluate the use of these multikinase inhibitors in this setting and to define overall survival, time to progression of disease, and adverse effects associated with therapy. Method(s): We conducted a retrospective cohort study of 71 patients treated with sorafenib (n = 57) and lenvatinib (n = 14) for advanced HCC at a Melbourne tertiary center from 2015 to 2020. Baseline demographic data, tumor characteristics, dosage, adverse effects, and survival from initiation of treatment were collected from medical chart review. Time to radiological and biochemical progression was also recorded. Result(s): In the sorafenib group, 70.18% of patients were classified as Child-Pugh A and 29.82% were classified as Child-Pugh B. A total of 73.68% of patients experienced any adverse effect, and 24.56% of patients experienced a severe grade 3 adverse effect, requiring cessation of therapy. The average number of days to radiological progression was 218.67 (median, 103; range, 21-996), which excluded three outliers who exhibitedspontaneous tumor regression. The average number of days to death from initiation of therapy was 341.86 (median, 196; range, 18-2061). Univariate analysis showed radiological progression was associated with higher Child-Pugh scores (odds ratio [OR], 2.4; P < 0.02), Model for End-Stage Liver Disease scores (OR, 2.96; P < 0.0045), dose reduction of sorafenib (OR, 2.4; P < 0.02), and presence of any adverse effect to therapy (OR, 2.0; P < 0.05). In the lenvatinib group, 50% of treated patients were classified as Child-Pugh B. A total of 85.70% had an adverse event. A subset of 42.85% of patients experienced severe grade 3 adverse effects. The average length of time to radiological progression was 119.14 days (median, 84; range, 24-346), and the average length of t

BACKGROUND: The Victorian Pancreas Cancer summit 2017 analysed state-wide data on management of Victorians with pancreas cancer between 2011 and 2015 to identify variations in care and outcomes. Pancreas cancer remains a formidable disease but systemic therapies are increasingly effective. Surgery remains essential but insufficient alone for cure. Understanding patterns of care and identifying variations in treatment is critical to improving outcomes. METHOD(S): This population-based study analysed data collected prospectively by Department of Health and Human services (Victorian state government). Data were extracted from Victorian Cancer Registry (covering all Victorian cancer diagnoses), Victorian Admitted-Episodes Dataset (all inpatient data), Victorian Radiotherapy Minimum Dataset and Victorian Death Index providing demographics, tumour and treatment characteristics, age-standardized incidence, overall and median survival. RESULT(S): Of 3962 Victorian patients with any form of pancreatic malignancy, 82% were ductal adenocarcinoma (PDAC), of whom 67% had metastases at diagnosis. One-year overall survival for PDAC was 30% (60% non-metastatic, 15% if metastatic). Median survival with metastases increased from 2.7 to 3.9 months, and from 13.3 to 15.9 months for non-metastatic PDAC between 2011 and 2015. Thirty-one percent of non-metastatic patients underwent pancreatectomy. About 1.5% were treated with neoadjuvant chemotherapy/chemoradiation. Of patients undergoing intended curative resection, 77% proceeded to adjuvant therapy. Fifty-one percent of metastatic PDAC patients never received anti-tumour therapy. CONCLUSION(S): Nearly one-fourth of surgically treated patients never received systemic therapy. More than two-thirds of non-metastatic patients never proceeded to surgery. Further consideration of neoadjuvant therapy should be given to borderline resectable patients. Most patients with PDAC still die soon after diagnosis, but median survival is increasing.Copy

BACKGROUND: The Victorian Pancreas Cancer summit 2017 analysed state-wide data on management of Victorians with pancreas cancer between 2011 and 2015 to identify variations in care and outcomes. Pancreas cancer remains a formidable disease but systemic therapies are increasingly effective. Surgery remains essential but insufficient alone for cure. Understanding patterns of care and identifying variations in treatment is critical to improving outcomes. METHOD(S): This population-based study analysed data collected prospectively by Department of Health and Human services (Victorian state government). Data were extracted from Victorian Cancer Registry (covering all Victorian cancer diagnoses), Victorian Admitted-Episodes Dataset (all inpatient data), Victorian Radiotherapy Minimum Dataset and Victorian Death Index providing demographics, tumour and treatment characteristics, age-standardized incidence, overall and median survival. RESULT(S): Of 3962 Victorian patients with any form of pancreatic malignancy, 82% were ductal adenocarcinoma (PDAC), of whom 67% had metastases at diagnosis. One-year overall survival for PDAC was 30% (60% non-metastatic, 15% if metastatic). Median survival with metastases increased from 2.7 to 3.9 months, and from 13.3 to 15.9 months for non-metastatic PDAC between 2011 and 2015. Thirty-one percent of non-metastatic patients underwent pancreatectomy. About 1.5% were treated with neoadjuvant chemotherapy/chemoradiation. Of patients undergoing intended curative resection, 77% proceeded to adjuvant therapy. Fifty-one percent of metastatic PDAC patients never received anti-tumour therapy. CONCLUSION(S): Nearly one-fourth of surgically treated patients never received systemic therapy. More than two-thirds of non-metastatic patients never proceeded to surgery. Further consideration of neoadjuvant therapy should be given to borderline resectable patients. Most patients with PDAC still die soon after diagnosis, but median survival is increasing.Copy

Background: The optimal duration of ACT following surgery for colon cancer remains controversial. SCOT is an international, randomised trial that compared 3 months versus 6 months of ACT in this setting. We sought the survival benefits that patients participating in SCOT judged necessary to make extra 3 months of ACT worthwhile. Method(s): SCOT participants from Australia & New Zealand completed a validated questionnaire 3 and 18 months after randomisation to elicit the minimum survival benefit each participant judged necessary to make it worthwhile having ACT for 6 months rather than 3 months. Standardised hypothetical scenarios used the following baseline survivals with 3 months of ACT: life expectancies (LE) of 5 years (5Y) and 15 years (15Y), and 5-year survival rates (5YS) of 65% and 85%. Comparisons were nonparametric, 2-sided, and considered statistically significant if p < 0.05. Result(s): Questionnaires were completed by 160 participants, 82 allocated 3 months ACT, and 78 allocated 6 months ACT. ACT was FOLFOX in 121 (75%), XELOX in 39 (25%), and the mean age was 64. Preferences varied substantially among participants, and did not differ according to the randomly allocated treatment group. The median survival benefits judged necessary to make the extra 3 months of ACT worthwhile were an extra: 3 years beyond a LE of 5Y; 3 years beyond a LE of 15Y; 15% beyond a 65% 5YS; and 5% beyond an 85% 5YS. Preferences were similar at 3 months and 18 months. Participants with symptomatic peripheral neuropathy (132, 82%) judged a median benefit of an extra 5% beyond a 65% 5YS necessary to warrant their symptoms. Conclusion(s): Participants' preferences varied substantially, and many judged much larger benefits needed to warrant having ACT for 6 months rather than 3 months than the estimates of the benefits based on the IDEA meta-analysis.

Background: In the ongoing phase 3 CheckMate 214 trial, nivolumab plus ipilimumab showed superior efficacy over sunitinib in patients with previously untreated intermediate-risk or poor-risk advanced renal cell carcinoma, with a manageable safety profile. In this study, we aimed to assess efficacy and safety after extended follow-up to inform the long-term clinical benefit of nivolumab plus ipilimumab versus sunitinib in this setting. Method(s): In the phase 3, randomised, controlled CheckMate 214 trial, patients aged 18 years and older with previously untreated, advanced, or metastatic histologically confirmed renal cell carcinoma with a clear-cell component were recruited from 175 hospitals and cancer centres in 28 countries. Patients were categorised by International Metastatic Renal Cell Carcinoma Database Consortium risk status into favourable-risk, intermediate-risk, and poor-risk subgroups and randomly assigned (1:1) to open-label nivolumab (3 mg/kg intravenously) plus ipilimumab (1 mg/kg intravenously) every 3 weeks for four doses, followed by nivolumab (3 mg/kg intravenously) every 2 weeks; or sunitinib (50 mg orally) once daily for 4 weeks (6-week cycle). Randomisation was done through an interactive voice response system, with a block size of four and stratified by risk status and geographical region. The co-primary endpoints for the trial were overall survival, progression-free survival per independent radiology review committee (IRRC), and objective responses per IRRC in intermediate-risk or poor-risk patients. Secondary endpoints were overall survival, progression-free survival per IRRC, and objective responses per IRRC in the intention-to-treat population, and adverse events in all treated patients. In this Article, we report overall survival, investigator-assessed progression-free survival, investigator-assessed objective response, characterisation of response, and safety after extended follow-up. Efficacy outcomes were assessed in all randomly assig

Background: In the ongoing phase 3 CheckMate 214 trial, nivolumab plus ipilimumab showed superior efficacy over sunitinib in patients with previously untreated intermediate-risk or poor-risk advanced renal cell carcinoma, with a manageable safety profile. In this study, we aimed to assess efficacy and safety after extended follow-up to inform the long-term clinical benefit of nivolumab plus ipilimumab versus sunitinib in this setting. Method(s): In the phase 3, randomised, controlled CheckMate 214 trial, patients aged 18 years and older with previously untreated, advanced, or metastatic histologically confirmed renal cell carcinoma with a clear-cell component were recruited from 175 hospitals and cancer centres in 28 countries. Patients were categorised by International Metastatic Renal Cell Carcinoma Database Consortium risk status into favourable-risk, intermediate-risk, and poor-risk subgroups and randomly assigned (1:1) to open-label nivolumab (3 mg/kg intravenously) plus ipilimumab (1 mg/kg intravenously) every 3 weeks for four doses, followed by nivolumab (3 mg/kg intravenously) every 2 weeks; or sunitinib (50 mg orally) once daily for 4 weeks (6-week cycle). Randomisation was done through an interactive voice response system, with a block size of four and stratified by risk status and geographical region. The co-primary endpoints for the trial were overall survival, progression-free survival per independent radiology review committee (IRRC), and objective responses per IRRC in intermediate-risk or poor-risk patients. Secondary endpoints were overall survival, progression-free survival per IRRC, and objective responses per IRRC in the intention-to-treat population, and adverse events in all treated patients. In this Article, we report overall survival, investigator-assessed progression-free survival, investigator-assessed objective response, characterisation of response, and safety after extended follow-up. Efficacy outcomes were assessed in all randomly assig

Background: The optimal duration of ACT following surgery for colon cancer remains controversial. SCOT is an international, randomised trial that compared 3 months versus 6 months of ACT in this setting. We sought the survival benefits that patients participating in SCOT judged necessary to make extra 3 months of ACT worthwhile. Method(s): SCOT participants from Australia & New Zealand completed a validated questionnaire 3 and 18 months after randomisation to elicit the minimum survival benefit each participant judged necessary to make it worthwhile having ACT for 6 months rather than 3 months. Standardised hypothetical scenarios used the following baseline survivals with 3 months of ACT: life expectancies (LE) of 5 years (5Y) and 15 years (15Y), and 5-year survival rates (5YS) of 65% and 85%. Comparisons were nonparametric, 2-sided, and considered statistically significant if p < 0.05. Result(s): Questionnaires were completed by 160 participants, 82 allocated 3 months ACT, and 78 allocated 6 months ACT. ACT was FOLFOX in 121 (75%), XELOX in 39 (25%), and the mean age was 64. Preferences varied substantially among participants, and did not differ according to the randomly allocated treatment group. The median survival benefits judged necessary to make the extra 3 months of ACT worthwhile were an extra: 3 years beyond a LE of 5Y; 3 years beyond a LE of 15Y; 15% beyond a 65% 5YS; and 5% beyond an 85% 5YS. Preferences were similar at 3 months and 18 months. Participants with symptomatic peripheral neuropathy (132, 82%) judged a median benefit of an extra 5% beyond a 65% 5YS necessary to warrant their symptoms. Conclusion(s): Participants' preferences varied substantially, and many judged much larger benefits needed to warrant having ACT for 6 months rather than 3 months than the estimates of the benefits based on the IDEA meta-analysis.

Purpose: Secondary CNS involvement (SCNS) is a profoundly adverse complication of diffuse large B-cell lymphoma. Evidence from older series indicated a median overall survival (OS) < 6 months; however, data from the immunochemotherapy era are limited. Method(s): Patients diagnosed with SCNS during or after first-line immunochemotherapy were identified from databases and/or regional/national registries from three continents. Clinical information was retrospectively collected from medical records. Result(s): In total, 291 patients with SCNS were included. SCNS occurred as part of first relapse in 254 (87%) patients and 113 (39%) had concurrent systemic relapse. With a median post-SCNS follow-up of 48 months, the median post-SCNS OS was 3.9 months and 2-year OS rate was 20% (95% CI: 15-25). In multivariable analysis of 173 patients treated with curative/intensive therapy (such as high-dose methotrexate [HDMTX] or platinum-containing regimens), age <=60 years, performance status 0-1, absence of combined leptomeningeal and parenchymal involvement, and SCNS occurring after completion of first-line therapy were associated with superior outcomes. Patients <=60 years with performance status 0-1 and treated with HDMTX-based regimens for isolated parenchymal SCNS had a 2-year OS of 62% (95% CI: 36-80). In patients with isolated SCNS, the addition of rituximab to HDMTX-based regimens was associated with improved OS. Amongst patients with isolated SCNS in CR following intensive treatment, high-dose chemotherapy and autologous stem cell transplantation did not improve OS (P = 0.9). Conclusion(s): In this large international cohort of patients treated with first-line immunochemotherapy, outcomes following SCNS remain poor. However, a moderate proportion of patients with isolated SCNS who received intensive therapies achieved durable remissions.Copyright © 2018 Elsevier Ltd

Aim: Primary central nervous system post-transplantation lymphoproliferative disorder (PCNS-PTLD) is a rare complication of immunosuppresion.Data is limited to case series, with median survival of 47 months reported in the literature. We aimed to identify our cases of PCNS-PTLD and describe clinical and pathological features and outcomes. Method(s): Search of Unit database and Australia and New Zealand Dialysis and Transplant Registry plus review of case records. We included recipients transplanted between 1990 and 2016 who were followed at our unit. Result(s): Ten patients with PCNS-PTLD and no evidence of systemic PTLD were identified and examined. Median age was 52 (range 31-79). Median time to diagnosis after transplant was 13 years (range 1-36). Pathology from cerebral biopsy showed Epstein-Barr virus (EBV)-positive large B cell lymphoma in all patients. Follow-up was complete for all but one patient (lost to followup since 2011). Of these, four died: one was palliated after diagnosis of PCNS-PTLD due to multiple comorbidities. Another withdrew treatment three years after diagnosis aged 82 due to frailty. A third nursing-home patient died three years following PTLD fromaspiration pneumonia. The forth patient withdrew dialysis after a prolonged admission from presumed progressive multifocal leukoencephalopathy 16 years post PTLD. Three patients remained in remission at time of death.All six surviving patients remain in remission and four retain graft function with a median eGFR of 54ml/min/1.73m2 (range 51-63). Two patients incurred graft loss, one at the time of PTLD diagnosis and the second at twelve months caused by chronic allograft nephropathy, however the second was re-transplanted 7 years after curative therapy. Treatment varied between patients and included surgical resection of single lesions, rituximab with systemic and/or intrathecal chemotherapy, localized or whole brain radiotherapy and reduction of immunosuppression. Conclusion(s): Over half PCNS-P

Purpose: Secondary CNS involvement (SCNS) is a profoundly adverse complication of diffuse large B-cell lymphoma. Evidence from older series indicated a median overall survival (OS) < 6 months; however, data from the immunochemotherapy era are limited. Method(s): Patients diagnosed with SCNS during or after first-line immunochemotherapy were identified from databases and/or regional/national registries from three continents. Clinical information was retrospectively collected from medical records. Result(s): In total, 291 patients with SCNS were included. SCNS occurred as part of first relapse in 254 (87%) patients and 113 (39%) had concurrent systemic relapse. With a median post-SCNS follow-up of 48 months, the median post-SCNS OS was 3.9 months and 2-year OS rate was 20% (95% CI: 15-25). In multivariable analysis of 173 patients treated with curative/intensive therapy (such as high-dose methotrexate [HDMTX] or platinum-containing regimens), age <=60 years, performance status 0-1, absence of combined leptomeningeal and parenchymal involvement, and SCNS occurring after completion of first-line therapy were associated with superior outcomes. Patients <=60 years with performance status 0-1 and treated with HDMTX-based regimens for isolated parenchymal SCNS had a 2-year OS of 62% (95% CI: 36-80). In patients with isolated SCNS, the addition of rituximab to HDMTX-based regimens was associated with improved OS. Amongst patients with isolated SCNS in CR following intensive treatment, high-dose chemotherapy and autologous stem cell transplantation did not improve OS (P = 0.9). Conclusion(s): In this large international cohort of patients treated with first-line immunochemotherapy, outcomes following SCNS remain poor. However, a moderate proportion of patients with isolated SCNS who received intensive therapies achieved durable remissions.Copyright © 2018 Elsevier Ltd

Aim: Primary central nervous system post-transplantation lymphoproliferative disorder (PCNS-PTLD) is a rare complication of immunosuppresion.Data is limited to case series, with median survival of 47 months reported in the literature. We aimed to identify our cases of PCNS-PTLD and describe clinical and pathological features and outcomes. Method(s): Search of Unit database and Australia and New Zealand Dialysis and Transplant Registry plus review of case records. We included recipients transplanted between 1990 and 2016 who were followed at our unit. Result(s): Ten patients with PCNS-PTLD and no evidence of systemic PTLD were identified and examined. Median age was 52 (range 31-79). Median time to diagnosis after transplant was 13 years (range 1-36). Pathology from cerebral biopsy showed Epstein-Barr virus (EBV)-positive large B cell lymphoma in all patients. Follow-up was complete for all but one patient (lost to followup since 2011). Of these, four died: one was palliated after diagnosis of PCNS-PTLD due to multiple comorbidities. Another withdrew treatment three years after diagnosis aged 82 due to frailty. A third nursing-home patient died three years following PTLD fromaspiration pneumonia. The forth patient withdrew dialysis after a prolonged admission from presumed progressive multifocal leukoencephalopathy 16 years post PTLD. Three patients remained in remission at time of death.All six surviving patients remain in remission and four retain graft function with a median eGFR of 54ml/min/1.73m2 (range 51-63). Two patients incurred graft loss, one at the time of PTLD diagnosis and the second at twelve months caused by chronic allograft nephropathy, however the second was re-transplanted 7 years after curative therapy. Treatment varied between patients and included surgical resection of single lesions, rituximab with systemic and/or intrathecal chemotherapy, localized or whole brain radiotherapy and reduction of immunosuppression. Conclusion(s): Over half PCNS-P

On behalf of the Australasian Gastro-Intestinal Trials Group (AGITG) Background: The optimal duration of ACT following surgery for colon cancer remains controversial. SCOT is an international, randomized trial that compared 3 versus 6 months ofACT in this setting.We sought the survival benefits that patients participating in SCOT judged necessary to make extra 3 months of ACT worthwhile. Method(s): SCOT participants from Australia and New Zealand completed a validated questionnaire 3 and 18 months after randomization to elicit the minimum survival benefit each participant judged necessary to make it worthwhile having ACT for 6 months rather than 3 months. Standardized hypothetical scenarios used the following baseline survivals with 3 months of ACT: life expectancies (LE) of 5 years (5Y) and 15 years (15Y), and 5-year survival rates (5YS) of 65% and 85%. Comparisons were non-parametric, two-sided and considered statistically significant if P < 0.05. Result(s): Questionnaires were completed by 160 participants, 82 allocated 3 months ACT and 78 allocated 6 months ACT. ACT was FOLFOX in 121 (75%), XELOX in 39 (25%) and the mean age was 64. Preferences varied substantially among participants, and did not dif-Editorialmaterial and organisationc 2018 JohnWiley & Sons Australia, Ltd. Copyright of individual abstracts remains with the authors fer according to the randomly allocated treatment group. The median survival benefits judged necessary to make the extra 3 months of ACT worthwhile were an extra: 3 years beyond an LE of 5Y; 3 years beyond an LE of 15Y; 15% beyond a 65% 5YS; and 5% beyond an 85% 5YS. Preferences were similar at 3 and 18 months. Participants with symptomatic peripheral neuropathy (132, 82%) judged a median benefit of an extra 5% beyond a 65% 5YS necessary to warrant their symptoms. Conclusion(s): Participants' preferences varied substantially, and many judged much larger benefits needed to warrant having ACT for 6 months rather than 3 months than the es

ObjectivesTo determine the effect of chronic disorders and their co-occurrence on survival and functioning in community-dwelling older adults. DesignPopulation-based cohort study. SettingKungsholmen, Stockholm, Sweden. ParticipantsIndividuals aged 78 and older examined by physicians four times over 11 years (N = 1,099). MeasurementsChronic diseases (grouped according to 10 organ systems according to the International Classification of Diseases, Tenth Revision, code) and multimorbidity (2 coexisting chronic diseases) were evaluated in terms of mortality, population attributable risk of death, median years of life lost, and median survival time with and without disability (need of assistance in 1 activities of daily living). ResultsApproximately one in four deaths were attributable to cardiovascular and one in six to neuropsychiatric diseases. Malignancy was the condition with the shortest survival time (2.5 years). Malignancies and cardiovascular disorders each accounted for approximately 5 years of life lost. In contrast, neurosensorial and neuropsychiatric conditions had the longest median survival time (>6 years), and affected people were disabled for more than half of this time. The most-prevalent and -burdensome condition was multimorbidity, affecting 70.4% of the population, accounting for 69.3% of total deaths, and causing 7.5 years of life lost. Finally, people with multimorbidity lived 81% of their remaining years of life with disability (median 5.2 years). ConclusionSurvival in older adults differs in length and quality depending on specific conditions. The greatest negative effect at the individual (shorter life, greater dependence) and societal (number of attributable deaths, years spent with disability) level was from multimorbidity, which has made multimorbidity a clinical and public health priority.

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: Many developed countries have identified the increasing incidence and mortality of hepatocellular carcinoma (HCC) as targets for intervention, with various preventive, early detection, and therapeutic options available. Current cost-benefit analyses that inform reimbursement of new therapeutic agents have been derived from administrative databases. We provide real-world costing for a clinical population of patients with HCC. Method(s): Patients were prospectively recruited over a 1-year period, in a previously published population-based clinical cohort from Melbourne, Australia. Direct costings were derived from hospitals for admissions, outpatients, and emergency attendance for 24 months of follow-up. Analysis was performed by phases of disease: initial phase (3 months before to 1 month after diagnosis), terminal phase (6 months before death), and continuing phase (time in between). Result(s): There were 136 patients from three tertiary hospitals, including the state liver transplant unit, representing 50% of the original cohort included in the costings. The total cost of treatment was $6 663 149 over 24 months, with a median total cost of $6046 in the initial phase, $33 737 in the continuing phase, and $19 395 in the terminal phase. The majority of costs were incurred by inpatient episodes (69%), with emergency attendance 22%, and outpatients 9%. Liver transplantation was most expensive overall, with best overall survival (21% of total costs, eight patients, median cost, $199 924; median survival, 24 months), followed by local ablation (19%, 20 patients, $31 011; 19 months), transarterial chemoembolization (15%, 24 patients, $41 576; 18 months), best supportive care (14%, 29 patients, $19 856; 3 months), resection (11%, 19 patients, $43 908; 20 months), and sorafenib (6%, 17 patients, $16 216; 13 months). Treatment received and Child-Pugh score at diagnosis were significant (P < 0.001) predictors of high cost on multivariate analysis. Tumor stage did

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: Many developed countries have identified the increasing incidence and mortality of hepatocellular carcinoma (HCC) as targets for intervention, with various preventive, early detection, and therapeutic options available. Current cost-benefit analyses that inform reimbursement of new therapeutic agents have been derived from administrative databases. We provide real-world costing for a clinical population of patients with HCC. Method(s): Patients were prospectively recruited over a 1-year period, in a previously published population-based clinical cohort from Melbourne, Australia. Direct costings were derived from hospitals for admissions, outpatients, and emergency attendance for 24 months of follow-up. Analysis was performed by phases of disease: initial phase (3 months before to 1 month after diagnosis), terminal phase (6 months before death), and continuing phase (time in between). Result(s): There were 136 patients from three tertiary hospitals, including the state liver transplant unit, representing 50% of the original cohort included in the costings. The total cost of treatment was $6 663 149 over 24 months, with a median total cost of $6046 in the initial phase, $33 737 in the continuing phase, and $19 395 in the terminal phase. The majority of costs were incurred by inpatient episodes (69%), with emergency attendance 22%, and outpatients 9%. Liver transplantation was most expensive overall, with best overall survival (21% of total costs, eight patients, median cost, $199 924; median survival, 24 months), followed by local ablation (19%, 20 patients, $31 011; 19 months), transarterial chemoembolization (15%, 24 patients, $41 576; 18 months), best supportive care (14%, 29 patients, $19 856; 3 months), resection (11%, 19 patients, $43 908; 20 months), and sorafenib (6%, 17 patients, $16 216; 13 months). Treatment received and Child-Pugh score at diagnosis were significant (P < 0.001) predictors of high cost on multivariate analysis. Tumor stage did

Background: Lowering serum uric acid concentrations is effective to control gout attack and prevent formation of tophi. Persistence with and adherence to uric acid lowering therapy are important to achieve benefit from medication. Therefore, insights into medication taking behaviour and factors influencing it, are extremely important. Objectives: To describe patterns of persistence with and adherence to allopurinol treatment among gout patients in the UK, and explore determinants of nonpersistence and non-adherence. Methods: A retrospective cohort study using the UK Clinical Practice Research Datalink (CPRD) was conducted. Patients with a first ever diagnosing coding for gout between 1st January 1987 and 30th June 2014 were included. Start of follow-up was defined as the first prescription of allopurinol after the start of valid data collection. Patients were excluded if they were younger than 40 years, were (ever) users of febuxostat and probenecid, or had a follow-up of less than 90 days after completion of the first prescription. Determinants included patient characteristics (at baseline), medication use (6 months prior to index-date) and other comorbidities (ever before index-date). Medication taking behaviour was described by non-persistence (occurrence of a first gap of 30 or 90 days) and non-adherence (proportion of days covered [PDC] over observation period) to allopurinol treatment. Kaplan Meier survival and multivariable Cox- and logistic regression were used to estimate the median time until discontinuation, and the strength of the association between determinants with non-persistence (90-day gap) and non-adherence, respectively. Results: A total of 47.744 gout patients (75.6% men; mean age 63.9 years) received allopurinol exclusively. After 5.3 years (SD 4.6) of follow-up 77% had a gap of 30-days and 54% had a gap of 90-days, and were non-persistence. Median survival time until discontinuation was 229 days (95% confidence interval [CI] 224 - 235) for a 3

Background/Purpose: Pulmonary arterial hypertension (PAH) is the leading cause of systemic sclerosis (SSc) related mortality. We sought to determine survival, predictors of mortality, and health related quality of life (HRQoL) of PAH in a large SSc cohort followed from the time of PAH diagnosis in the modern era of PAH-specific vasodilator therapy. Method(s): Patients enrolled in a SSc longitudinal cohort between 2009 - 2015 were included. Group 1 PAH was diagnosed on right heart catheterization (RHC) (mPAP >=25 and PAWP <15 mmHg). Other causes of pulmonary hypertension were excluded. Summary statistics, chi-square tests and survival methods were used to determine survival rates and identify predictors of mortality. HRQoL was measured using the Medical Outcomes Study Short Form 36 (SF-36). Result(s): Among 132 SSc-PAH patients, 84.9% were female and 68.9% had limited disease subtype. The mean (+/-SD) age at diagnosis of PAH was 62.3 (+/-10.5) years and disease duration at PAH diagnosis was 14.1 (+/-11.9) years. Over a median (IQR) follow-up of 3.7 (1.6- 5.8) years, 60 (45.5%) patients died, with a median survival time from PAH diagnosis of 3.7 years. The standardized mortality ratio for patients with SSc-PAH compared with the general population was 5.8 (95%CI 4.3-7.8). The years of life lost with SSc-PAH was 15.22 years (95%CI 12.3-18.1). Kaplan-Meier survival curves (Figure 1) showed a survival advantage with combination PAH therapy and anticoagulation. Older age at PAH diagnosis (p=0.03), coexistence of mild ILD (p=0.01), worse WHO functional class (p=0.03), higher mean pulmonary arterial pressure at PAH diagnosis (p=0.001) and presence of digital ulcers (p=0.01) during follow-up were predictive of PAH mortality (Table 1). Combination therapy together with anticoagulation provided the most significant survival advantage, with a 72% reduction in mortality compared with pulmonary vasodilator monotherapy without anticoagulation (Figure 1). Patients with SSc-PAH had c

Objective: Sorafenib is an oral multikinase inhibitor that improves survival in advanced hepatocellular carcinoma (HCC). In the absence of alternative therapies, sorafenib is often continued despite advancing liver disease or tumour progression. Real world studies are important to better characterise outcomes in these populations. Our aim was to review patterns of sorafenib use across eight Australian tertiary hospitals, defining variables associated with clinical outcomes. Material(s) and Method(s): Retrospective cohort study of medical records of 320 patients treated with sorafenib for HCC. Baseline clinical parameters, dosage, adverse effects, and survival from initiation of treatment were collected. Time to radiological progression and 3-month alpha-fetoprotein (AFP) levels were available for a subset of patients. Result(s): Adverse effects occurred in 79% of patients, requiring dose reduction in 31% of patients. Multivariate analysis identified an increased rate of mortality with Child-Pugh C (HR 5.52, p = 0.012), ECOG performance status 2-3 (HR 2.84, p = 0.001), and extrahepatic metastases (HR 1.54, p = 0.04), and decreased rate of mortality with an AFP reduction of at least 20% at 3 months (HR 0.38, p = 0.001). An increased rate of radiological progression was associated with ECOG performance status 2-3 (HR 2.34, p = 0.041), whilst a decreased rate of radiological progression was associated with development of on-treatment diarrhoea (HR 0.55, p = 0.015). Conclusion(s): Survival in patients with Child-Pugh C liver function or advanced functional impairment treated with sorafenib is poor and thus routine use of this agent in these patients does not appear justified, particularly given the high rate of adverse effects. AFP concentration on therapy may help identify favourable response to treatment.Copyright © 2016 Informa UK Limited, trading as Taylor & Francis Group.

Background/Purpose: Pulmonary arterial hypertension (PAH) is the leading cause of systemic sclerosis (SSc) related mortality. We sought to determine survival, predictors of mortality, and health related quality of life (HRQoL) of PAH in a large SSc cohort followed from the time of PAH diagnosis in the modern era of PAH-specific vasodilator therapy. Method(s): Patients enrolled in a SSc longitudinal cohort between 2009 - 2015 were included. Group 1 PAH was diagnosed on right heart catheterization (RHC) (mPAP >=25 and PAWP <15 mmHg). Other causes of pulmonary hypertension were excluded. Summary statistics, chi-square tests and survival methods were used to determine survival rates and identify predictors of mortality. HRQoL was measured using the Medical Outcomes Study Short Form 36 (SF-36). Result(s): Among 132 SSc-PAH patients, 84.9% were female and 68.9% had limited disease subtype. The mean (+/-SD) age at diagnosis of PAH was 62.3 (+/-10.5) years and disease duration at PAH diagnosis was 14.1 (+/-11.9) years. Over a median (IQR) follow-up of 3.7 (1.6- 5.8) years, 60 (45.5%) patients died, with a median survival time from PAH diagnosis of 3.7 years. The standardized mortality ratio for patients with SSc-PAH compared with the general population was 5.8 (95%CI 4.3-7.8). The years of life lost with SSc-PAH was 15.22 years (95%CI 12.3-18.1). Kaplan-Meier survival curves (Figure 1) showed a survival advantage with combination PAH therapy and anticoagulation. Older age at PAH diagnosis (p=0.03), coexistence of mild ILD (p=0.01), worse WHO functional class (p=0.03), higher mean pulmonary arterial pressure at PAH diagnosis (p=0.001) and presence of digital ulcers (p=0.01) during follow-up were predictive of PAH mortality (Table 1). Combination therapy together with anticoagulation provided the most significant survival advantage, with a 72% reduction in mortality compared with pulmonary vasodilator monotherapy without anticoagulation (Figure 1). Patients with SSc-PAH had c

Objective: Sorafenib is an oral multikinase inhibitor that improves survival in advanced hepatocellular carcinoma (HCC). In the absence of alternative therapies, sorafenib is often continued despite advancing liver disease or tumour progression. Real world studies are important to better characterise outcomes in these populations. Our aim was to review patterns of sorafenib use across eight Australian tertiary hospitals, defining variables associated with clinical outcomes. Material(s) and Method(s): Retrospective cohort study of medical records of 320 patients treated with sorafenib for HCC. Baseline clinical parameters, dosage, adverse effects, and survival from initiation of treatment were collected. Time to radiological progression and 3-month alpha-fetoprotein (AFP) levels were available for a subset of patients. Result(s): Adverse effects occurred in 79% of patients, requiring dose reduction in 31% of patients. Multivariate analysis identified an increased rate of mortality with Child-Pugh C (HR 5.52, p = 0.012), ECOG performance status 2-3 (HR 2.84, p = 0.001), and extrahepatic metastases (HR 1.54, p = 0.04), and decreased rate of mortality with an AFP reduction of at least 20% at 3 months (HR 0.38, p = 0.001). An increased rate of radiological progression was associated with ECOG performance status 2-3 (HR 2.34, p = 0.041), whilst a decreased rate of radiological progression was associated with development of on-treatment diarrhoea (HR 0.55, p = 0.015). Conclusion(s): Survival in patients with Child-Pugh C liver function or advanced functional impairment treated with sorafenib is poor and thus routine use of this agent in these patients does not appear justified, particularly given the high rate of adverse effects. AFP concentration on therapy may help identify favourable response to treatment.Copyright © 2016 Informa UK Limited, trading as Taylor & Francis Group.

Bayesian nonparametric inferential procedures based on Markov chain Monte Carlo marginal methods typically yield point estimates in the form of posterior expectations. Though very useful and easy to implement in a variety of statistical problems, these methods may suffer from some limitations if used to estimate non-linear functionals of the posterior distribution. The main goal is to develop a novel methodology that extends a well-established marginal procedure designed for hazard mixture models, in order to draw approximate inference on survival functions that is not limited to the posterior mean but includes, as remarkable examples, credible intervals and median survival time. The proposed approach relies on a characterization of the posterior moments that, in turn, is used to approximate the posterior distribution by means of a technique based on Jacobi polynomials. The inferential performance of this methodology is analyzed by means of an extensive study of simulated data and real data consisting of leukemia remission times. Although tailored to the survival analysis context, the proposed procedure can be adapted to a range of other models for which moments of the posterior distribution can be estimated.

Bayesian nonparametric marginal methods are very popular since they lead to fairly easy implementation due to the formal marginalization of the infinitedimensional parameter of the model. However, the straightforwardness of these methods also entails some limitations. They typically yield point estimates in the form of posterior expectations, but cannot be used to estimate non-linear functional of the posterior distribution, such as median, mode or credible intervals. This is particularly relevant in survival analysis where non-linear functionals such as the median survival time play a central role for clinicians and practitioners. The main goal of this paper is to summarize the methodology introduced in (Arbel, Lijoi and Nipoti, Comput. Stat. Data. Anal. 2015) for hazard mixture models in order to draw approximate Bayesian inference on survival functions that is not limited to the posterior mean. In addition, we propose a practical implementation of an R package called momentify designed for moment-based density approximation. By means of an extensive simulation study, we thoroughly compare the introduced methodology with standard marginal methods and empirical estimation.

Early detection of breast cancer is an important public health policy. Programs of regular screening examinations have been widely established in an attempt to detect the disease when the primary tumour diameter is small. In South Australia, BreastScreen SA suggests that women between the ages of 50 and 70 years be screened every 24 months. Our aim in this paper is to make assessments of various screening procedures by using statistical models with parameters estimated exclusively from South Australian data. We establish a relationship between primary tumour diameter and ultimate survival time. We estimate an advantage of 2.9 (.7) years in median survival time for those women detected with the disease by BreastScreen SA, compared with an unscreened population. We construct a computer model from which we determine the consequences of using a 12 month screening interval, and also the effect of beginning screening at the age of 40 rather than the current conventional commencement age of 50 years.