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Introduction: The COVID‐19 pandemic caused rapid implementation of telehealth for melanoma follow‐up care in Australia. This study explores Australian melanoma patients and clinicians' level of satisfaction with telehealth. Methods: A cross‐sectional study was conducted across three specialist melanoma centres in Sydney, Australia. Melanoma patients (all stages) and clinicians completed mixed methods surveys seeking socio‐demographic and clinical information and questionnaires to assess satisfaction with telehealth. Additionally, patients completed measures of quality of life, fear of cancer recurrence and trust in their oncologist. Patients and clinicians provided open‐ended responses to qualitative questions about their perceptions of telehealth. Results: One hundred and fifteen patients and 13 clinicians responded to surveys. Telephone was used by 109 (95%) patients and 11 (85%) clinicians. Fifty‐seven (50%) patients and nine (69%) clinicians preferred face‐to‐face consultations, 38 (33%) patients and 3 (23%) clinicians preferred a combination of face‐to‐face and telehealth consultations. Five (4%) patients and nil clinicians preferred telehealth consultations. Patients diagnosed with early‐stage melanoma, using telehealth for the first time, who have lower trust in their oncologist, and having higher care delivery, communication and supportive care concerns were likely to report lower satisfaction with telehealth. Open‐ended responses were consistent between patients and clinicians, who reported safety, convenience and improved access to care as major benefits, while identifying personal, interpersonal, clinical and system‐related disadvantages. Discussion: While telehealth has been widely implemented during COVID‐19, the benefits identified by patients and clinicians may extend past the pandemic. Telehealth may be considered for use in conjunction with face‐to‐face consultations to provide melanoma follow‐up care. [ABSTRACT FROM AUTHOR]

Aims and Objectives: The study investigated: (a) the usage patterns of paracetamol, and (b) the association between paracetamol use and patient outcomes such as liver and kidney functions among older people. Background: Paracetamol is a well‐known analgesic and antipyretic drug, with an excellent safety profile when used within its recommended dose. It is a commonly used drug by people aged over 65 years to treat chronic pain. Prolonged use of paracetamol in the elderly is poorly understood. As such, there is a genuine risk among older people of unintentional overdose. Methods: A retrospective analysis of medical records in rehabilitation wards was undertaken from 1 July 2016 to 30 June 2017. Patients' paracetamol use, prescribing patterns and biochemical results were analysed to assess for differences in admission and discharge biochemistry results. The TREND Statement was utilised to guide study reporting (Enhancing the QUAlity and Transparency Of health Research, 2021). Results: A total of 1119 patients were admitted for seven or more days in a metropolitan tertiary hospital in Melbourne. Almost three‐quarters (74%) of patients were administered paracetamol; 76.1% received 'Immediate‐Release Paracetamol' (IRP), and 23.9% were given 'Sustained‐Release Paracetamol' (SRP). A proportion (4.5%) of patients in both the IRP and SRP groups received more than the daily recommended dose. There were limited statistically significant differences between patients' admission and discharge biochemistry results; group or time differences were observed, which were indicative of improvements within the paracetamol group. Conclusion: Paracetamol was a commonly used medication among long‐stay elderly patients. Precaution to ensure paracetamol use does not exceed recommended daily doses is required. This study suggests that paracetamol used at a therapeutic level in older patients had limited, negative associations with liver and kidney function. Relevance to clinical practice: The clinical practice regarding prolonged use of paracetamol is ambitious. The increased risk of paracetamol toxicity among the frail elderly is a concern. Optimising the dose adjustment in the elderly is important to avoid adverse outcomes. [ABSTRACT FROM AUTHOR]

Chickpea (Cicer arietinum) is a major legume crop, with Australia being the second largest producer worldwide. Pratylenchus neglectus is a root‐lesion nematode that invades, feeds and reproduces in roots of pulse and cereal crops. In Australia, chickpea and wheat (Triticum aestivum) are commonly grown in rotation and annual damage by P. neglectus accounts for large economic losses to both crops. Cultivated chickpea has narrow genetic diversity that limits the potential for improvement in resistance breeding. New collections of wild chickpea species, C. reticulatum and C. echinospermum, have substantially increased the previously limited world collection of wild Cicer germplasm and offer potential to widen the genetic diversity of cultivated chickpea through the identification of accessions with good resistance. This research assessed 243 C. reticulatum and 86 C. echinospermum accessions for response to P. neglectus in replicated experiments under controlled glasshouse conditions from 2013 and 2014 collection missions that were received, tested and analysed in two experimental sets. Multi‐experiment analyses showed lower P. neglectus population densities in both sets of wild Cicer accessions tested than Australia's elite breeding cultivar PBA HatTrick at the significance level p < 0.05. Provisional resistance ratings were given to all genotypes tested in both experimental sets, with C. reticulatum accessions CudiB_008B and Kayat_066 rated as resistant in both Set 1 and Set 2. New sources of resistance to P. neglectus observed in this study can be introgressed into commercial chickpea cultivars to improve their resistance to this nematode. [ABSTRACT FROM AUTHOR]

Australia and New Zealand have the highest incidence and mortality rates for melanoma in the world. Local surgery is still the standard treatment of primary cutaneous melanoma, and it is therefore important that surgeons understand the optimal care pathways for patients with melanoma. Accurate staging is critical to ensure a reliable assessment of prognosis and to guide treatment selection. Sentinel node biopsy (SNB) plays an important role in staging and the provision of reliable prognostic estimates for patients with cutaneous melanoma. Patients with stage III melanoma have a substantial risk of disease recurrence following surgery, leading to poor long-term outcomes. Systemic immunotherapies and targeted therapies, known to be effective for stage IV melanoma, have now also been shown to be effective as adjuvant post-surgical treatments for resected stage III melanoma. These patients should be made aware of this and preferably managed in an integrated multidisciplinary model of care, involving the surgeon, medical oncologists and radiation oncologists. This review considers the impact of a recent update to the American Joint Committee on Cancer (AJCC) staging system, the role of SNB for patients with high-risk primary melanoma and recent advances in adjuvant systemic therapies for high-risk patients. [ABSTRACT FROM AUTHOR]

Aim: To develop focused priorities to inform the revision of Australia's Sudden Unexpected Death in Infancy (SUDI) risk reduction public health programme. Methods: A content expert consensus research activity was designed using two consensus techniques. The two‐phase study employed a Delphi process (phase 1) and a Nominal Group workshop technique (phase 2). The Delphi invited 56 national and international content experts. The Nominal Group comprised 17 Australasian experts and stakeholders to ensure priority setting was relevant to the Australian context. Results: Phase 1 established a ranked thematic list of 10 key SUDI risk reduction themes. Phase 2 addressed three nominal questions producing prioritised lists for: key‐message wording; contextual information and strategies to support caregiver implementation of key messages; and considerations in redesigning and dissemination of a safe sleep campaign. The top four priority themes were: sleep position, sleep space, smoking and surface‐sharing. Conclusion: This two‐phase priority setting was successful in establishing clearly defined infant safe sleep priorities. International content expert participation in phase 1 strengthened priority setting outcomes while phase 2 ensured final outcomes provided a strong national focus reflective of identified needs of Australian families. Findings provide a foundation from which important components can be considered when revising and developing future SUDI risk reduction programmes. [ABSTRACT FROM AUTHOR]

Aim: To examine differences in the prevalence of risk factors for sudden unexpected death in infancy (SUDI) between Aboriginal and Torres Strait Islander and non‐Indigenous infants. Methods: A retrospective cohort study of SUDI in Queensland during 2010‐2014 examined exposure to SUDI risk factors, to identify factors accounting for higher SUDI mortality among Indigenous infants. A multistage algorithm was applied to linked data to determine Indigenous status. Results: There were 228 SUDI, of which Indigenous infants comprised 26.8%. The Indigenous SUDI rate was 2.13/1000 live births compared to 0.72/1000 for non‐Indigenous. The disparity between Indigenous and non‐Indigenous SUDI was accounted for by surface sharing (OR = 2.93 95% CI = 1.41, 6.07), smoking (OR = 2.49, 95% CI = 1.13, 5.52), and a combination of background antenatal and sociodemographic factors (inadequate antenatal care [OR = 6.93, 95% CI = 2.20, 21.86], young maternal age at first birth [OR = 4.02, 95% CI = 1.49, 10.80] and outer regional [OR = 3.03, 95% CI = 1.37, 6.72] and remote locations [OR = 11.31, 95% CI = 3.47, 36.83]). Conclusion: Culturally responsive prevention efforts, including wrap‐around maternity care and strategies that reduce maternal smoking and promote safer yet culturally acceptable ways of surface sharing, may reduce Indigenous SUDI mortality. [ABSTRACT FROM AUTHOR]

Background: Globally, the incidence of sleep-related infant mortality declined dramatically following the first public health campaigns seen internationally in the 1990s to reduce the risks of sudden infant death. However, Australian Sudden Unexpected Death in Infancy (SUDI) rates have plateaued with little change in incidence since 2004 despite two further public health safe sleep campaigns. This study aims to describe contemporary infant care practices employed by families related to the current public health SUDI prevention program.Methods: A cross-sectional survey of 3341 Queensland primary caregivers with infants approximately 3-months of age was conducted using the Queensland Registry of Births, Deaths and Marriages as a sampling frame. Surveys were returned either via reply-paid mail or online. Questionnaires explored prevalence of infant care practices and awareness of safe sleep recommendations. Univariable analysis was used to generate descriptive statistics for key variables.Results: Overall, only 13% of families routinely practised all six 'Safe Sleeping' program messages. More than one third (1118, 34%) of infants had slept in a non-supine sleep position at some time. Potentially hazardous sleep environments were common, with 38% of infants sleeping with soft items or bulky bedding, or on soft surfaces. Nearly half, for either day- or night-time sleeps, were routinely placed in a sleep environment that was not designed or recommended for safe infant sleep (i.e. a bouncer, pram, beanbag). Most babies (84%) were reportedly smoke free before and after birth. Sleeping in the same room as their caregiver for night-time sleeps was usual practice for 75% of babies. Half (1600, 50%) of all babies shared a sleep surface in the last two-weeks. At 8-weeks, 17% of infants were no longer receiving any breastmilk.Conclusions: The prevalence rates of infant care practices among this Australian population demonstrate many families continue to employ suboptimal practices despite Australia's current safe sleep campaign. Strategic approaches together with informed decisions about pertinent messages to feature within future public health campaigns and government policies are required so targeted support can be provided to families with young infants to aid the translation of safe sleep evidence into safe sleeping practices. [ABSTRACT FROM AUTHOR]

Describes the development and current status of a microfilming project of Australian historical records held in various repositories throughout the United Kingdom. (RAO)

Background/Objectives: There are limited population‐based data documenting the incidence and management of lentigo maligna (LM) and invasive lentigo maligna melanoma (LMM). We report the data on occurrence and management of LM and LMM in an Australian population. Methods: Prospective collection of incidence and clinician‐reported management of melanoma in situ (MIS; n = 450, capped) and localised invasive melanoma (n = 3251) notified to the New South Wales Cancer Registry over 12‐months in 2006–2007. Results: The estimated annual incidence of all MIS was 27.0 per 100 000 (LM 12.2, non‐LM MIS 5.9 and unclassified MIS 9.0). Patients with LM or LMM were on average approximately 10 years older than those with other melanoma subtypes (P < 0.001). The head and neck was the location of 59% of LM, 44% of LMM and <20% of other melanoma subtypes (P < 0.001). The majority of LM and LMM were treated only by specialists. Diagnostic partial biopsies were more frequent for LM and LMM than for other melanoma subtypes, and primary care physicians were more likely than specialists to do a punch partial biopsy than a shave biopsy. The reported median definitive excision margin for LM was 5.0 mm compared with 7.2 mm for non‐LM MIS (P = 0.001). Conclusions: In this Australian population, LM was twice as frequent as other types of MIS. Improved strategies for diagnosis and management are required. [ABSTRACT FROM AUTHOR]

Introduction: The evidence-based national clinical practice guidelines for the management of cutaneous melanoma published in 2008 are currently being updated. This article summarises the findings from multiple chapters of the guidelines on different methods of melanoma detection and of monitoring the skin for patients at high risk of melanoma. Early detection of melanoma is critical, as thinner tumours are associated with enhanced survival; therefore, strategies to improve early detection are important to reduce melanoma-related mortality.Main Recommendations: Clinicians who perform skin examinations for the purpose of detecting skin cancer should be trained in and use dermoscopy. The use of short term sequential digital dermoscopy imaging to detect melanomas that lack dermoscopic features of melanoma is recommended to assess individual melanocytic lesions of concern. The use of long term sequential digital dermoscopy imaging to detect melanomas that lack dermoscopic features of melanoma is recommended to assess individual or multiple melanocytic lesions for routine surveillance of high risk patients. The use of total body photography should be considered in managing patients at increased risk for melanoma, particularly those with high naevus counts and dysplastic naevi. There is insufficient evidence to recommend the routine use of automated instruments for the clinical diagnosis of primary melanoma.Management Overview: Determining the relative indications for each diagnostic method and how each method should be introduced into the surveillance of a patient requires careful consideration and an individualised approach. [ABSTRACT FROM AUTHOR]

Introduction: Definitive management of primary cutaneous melanoma consists of surgical excision of the melanoma with the aim of curing the patient. The melanoma is widely excised together with a safety margin of surrounding skin and subcutaneous tissue, after the diagnosis and Breslow thickness have been established by histological assessment of the initial excision biopsy specimen. Sentinel lymph node biopsy should be discussed for melanomas ≥ 1 mm thickness (≥ 0.8 mm if other high risk features) in which case lymphoscintigraphy must be performed before wider excision of the primary melanoma site. The 2008 evidence-based clinical practice guidelines for the management of melanoma (http://www.cancer.org.au/content/pdf/HealthProfessionals/ClinicalGuidelines/ClinicalPracticeGuidelines-ManagementofMelanoma.pdf) are currently being revised and updated in a staged process by a multidisciplinary working party established by Cancer Council Australia. The guidelines for definitive excision margins for primary melanomas have been revised as part of this process. Main recommendations: The recommendations for definitive wide local excision of primary cutaneous melanoma are: melanoma in situ: 5-10 mm margins invasive melanoma (pT1) ≤ 1.0 mm thick: 1 cm margins invasive melanoma (pT2) 1.01-2.00 mm thick: 1-2 cm margins invasive melanoma (pT3) 2.01-4.00 mm thick: 1-2 cm margins invasive melanoma (pT4) > 4.0 mm thick: 2 cm margins Changes in management as a result of the guideline: Based on currently available evidence, excision margins for invasive melanoma have been left unchanged compared with the 2008 guidelines. However, melanoma in situ should be excised with 5-10 mm margins, with the aim of achieving complete histological clearance. Minimum clearances from all margins should be assessed and stated. Consideration should be given to further excision if necessary; positive or close histological margins are unacceptable. [ABSTRACT FROM AUTHOR]

Problems often arise in cases of lethal inflicted injury in infants and children in determining the chronology of events. However, on occasion it may be assumed that a parent's statement that the child appeared normal at a particular time is correct. It is then inferred that the lethal injury occurred after this time. In a study of infants from Queensland, Australia a significant number of cases occurred where a parent/carer did not actually recognise that an infant was deceased or in extremis despite handling of the infants, some of whom had established rigor mortis. Assessment of their infant's health status was quite flawed, presumably due to inattention, fatigue, or confirmatory bias (seeing what is expected). This could also apply to infants with head injuries who may manifest quite non-specific signs such as lethargy, somnolence or alteration in conscious state, manifestations that could easily be confused with normal drowsiness or sleep. Thus, the evaluation of parent/carer statements must be tempered by the knowledge that their opinions may not always (for completely understandable reasons) be reliable, and should not be uncritically accepted as a basis for deciding the time course for a lethal process. [ABSTRACT FROM AUTHOR]

The incidence and prognosis of cutaneous melanoma in children under 13 years of age has always been difficult to assess. The main reasons for this difficulty include the rarity of melanoma in children, referral biases from investigating institutions, changing conceptions in the histological diagnosis of true melanoma, and the lack of large enough study groups with sufficient follow-up to estimate 10-year survival rates. The present study documents 32 cases of childhood cutaneous melanoma drawn from the records of two large referral centres in New South Wales, Australia: the Sydney Melanoma Unit and the Newcastle Melanoma Unit in order to demonstrate some of the difficulties in the assessment of incidence and prognosis in children. [ABSTRACT FROM AUTHOR]

Pratylenchus thornei, a nematode species that feeds and reproduces in chickpea (Cicer arietinum) roots, is widespread throughout the Mediterranean basin and Indian subcontinent. In Australia, it can cause yield losses up to approximately 25% of intolerant chickpea cultivars. Potential for improvement has been hindered by the narrow genetic diversity of cultivated chickpea and a limited world collection of original wild Cicer spp. in the primary gene pool, consisting of 18 C. reticulatum and 10 C. echinospermum accessions. Recently, collections of C. reticulatum and C. echinospermum from Turkey have substantially increased the number of accessions. This study evaluated 133 C. reticulatum and 41 C. echinospermum accessions from the new collection for resistance to P. thornei under controlled conditions in repeated glasshouse pot experiments. The aim of the study was to identify accessions with resistance superior to that currently available in Australian germplasm. Both wild Cicer spp. were found, on average, to be more resistant to P. thornei (P < 0.001) than C. arietinum. Combined analyses across experiments to determine genetic rankings showed that 13 (7%) wild accessions were significantly more resistant than the most resistant C. echinospermum reference ILWC 246. while another 40 (23%) accessions were significantly more resistant than the least susceptible Australian chickpea cultivar PBA Seamer. Mean P. thornei population densities differed significantly between collection sites in Turkey and within each of the genetic population groups. The sites Kayatepe and Baristepel. and genetic population groups Ret_A and Ret_F associated with sites Oyali and Baristepel. produced the lowest P. thornei population densities. This is the first report assessing the resistance to P. thornei of this new collection which offers novel sources of P. thornei resistance and untapped genetic diversity valuable for international chickpea breeding programs to exploit. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented about a case of regressing metastatic melanoma and depigmentation with characteristics similar to vitiligo in an Indigenous Australian man.

This study sought to assess whether the interval between diagnostic excision-biopsy of a primary melanoma and definitive wide excision with sentinel node biopsy (SNB) influenced the size of SN metastatic deposits, which might have implications for management and prognosis. Data were collected for (i) a Dutch population-based cohort of patients treated between 2004 and 2014 who underwent SNB within 100 days of complete excision of their primary melanoma and who were SN-positive with known SN metastasis diameter (n = 1027) and (ii) a cohort from a large Australian melanoma treatment centre (n = 541) who presented in the same time period. The effects of SNB timing on the size of SN metastatic deposits were analysed. Dutch patients whose SNB was performed in the second or third months after diagnosis had significantly larger SN metastasis diameters than patients who had their SNB in the first month (median increases of 17% (95%CI -14, 60%, p = 0.211) and 71% (95%CI 15, 119%, p = 0.004), respectively). No significant difference in tumour diameter for early and late SNB was found in the Australian cohort. SN metastasis diameter became progressively greater with SN biopsy in the second and third months after primary melanoma diagnosis in the larger, population-based patient cohort. An increase in metastasis diameter was not observed in the smaller, institutional cohort, possibly due to detection of larger SN metastases by routine pre-operative ultrasound, with fine-needle biopsy confirmation. These patients did not proceed to SNB and were therefore not included in the study. • The interval between melanoma diagnosis and sentinel node (SN) biopsy varies greatly. • This study examined the association between that time interval and SN tumour size. • An effect on SN tumour size was found in only the larger of two patient cohorts. • The effect of delayed SN biopsy on metastasis size requires further study. [ABSTRACT FROM AUTHOR]

The brain is a common site of metastatic disease for patients with advanced melanoma. Brain metastasis portends a poor prognosis, often causing deterioration in neurological function and quality of life, and leading to neurological death. Treatment approaches including surgery, radiotherapy and systemic therapy can lead to better control of this problem. Therefore, appropriate guidelines for the management of melanoma brain metastases need to be established, with regular updating when new treatment options become available. A multidisciplinary working party established by Cancer Council Australia has produced up-to-date, evidence-based clinical practice guidelines for the management of melanoma. After selecting key clinical questions, a comprehensive literature search for relevant studies was conducted, followed by systematic review of those studies. Data were summarised and the evidence was assessed, leading to the development of recommendations. Symptomatic lesions are best treated with surgery, when possible; this provides safe and effective local control. For patients with single or a small number of asymptomatic brain metastases, stereotactic radiotherapy is recommended, but in asymptomatic patients who have not previously received systemic treatment, drug therapy can be considered as a first-line treatment option. Whole brain radiotherapy may provide palliative benefits in patients with multiple brain metastases. Whenever possible, melanoma patients with brain metastases should be managed by a multidisciplinary team of melanoma specialists that considers the optimal combination and sequencing of surgery, radiotherapy and systemic therapy. • This study provides evidence-based guidelines for the management of melanoma brain metastases. • The melanoma multidisciplinary team must consider the optimal treatment combination. • Symptomatic lesions are best treated with surgery. • Stereotactic radiosurgery can be recommended for small number of metastases. • In asymptomatic patients, drug therapy can be considered as a first-line treatment. [ABSTRACT FROM AUTHOR]

Background: Adjuvant dabrafenib plus trametinib therapy improves relapse-free survival in patients with resected stage III melanoma. We aimed to ascertain the proportion of patients who would have a pathological response and a response according to Response Evaluation Criteria in Solid Tumors (RECIST) after neoadjuvant dabrafenib plus trametinib therapy for resectable clinical stage III melanoma.Methods: NeoCombi was a single-arm, open-label, single-centre, phase 2 study done at Melanoma Institute Australia (Sydney, NSW, Australia). Eligible patients were adults (aged ≥18 years) with histologically confirmed, resectable, RECIST-measurable, clinical stage IIIB-C (American Joint Committee on Cancer [AJCC] 7th edition), BRAFV600-mutant melanoma, and had an Eastern Cooperative Oncology Group performance status of 1 or lower. Patients received 150 mg dabrafenib orally, twice daily, plus 2 mg trametinib orally, once daily, for 52 weeks (12 weeks of neoadjuvant therapy before complete resection of the pre-therapy tumour bed, and 40 weeks of adjuvant therapy thereafter). CT and PET scans were done at baseline and before resection. The primary outcomes were the proportion of patients achieving a complete pathological response and the proportion of patients achieving a response according to RECIST at week 12, analysed as per protocol. This trial is registered with ClinicalTrials.gov, NCT01972347, and follow-up of patients is ongoing.Findings: Between Aug 20, 2014, and April 19, 2017, 40 patients were screened, of whom 35 eligible patients were enrolled, received neoadjuvant dabrafenib plus trametinib, and underwent resection. At the data cutoff (Sept 24, 2018), median follow-up was 27 months (IQR 21-36). At resection, 30 (86%) patients achieved a RECIST response; 16 (46%; 95% CI 29-63) had a complete response and 14 (40%; 24-58) had a partial response. Five patients (14%; 95% CI 5-30) had stable disease, and no patients progressed. After resection and pathological evaluation, all 35 patients achieved a pathological response, of whom 17 (49%; 95% CI 31-66) patients had a complete pathological response and 18 (51%; 95% CI 34-69) had a non-complete pathological response. Treatment-related serious adverse events occurred in six (17%) of 35 patients and grade 3-4 adverse events occurred in ten (29%) patients. No treatment-related deaths were reported.Interpretation: Neoadjuvant dabrafenib plus trametinib therapy could be considered in the management of RECIST-measurable resectable stage III melanoma as it led to a high proportion of patients achieving a complete response according to RECIST and a high proportion of patients achieving a complete pathological response, with no progression during neoadjuvant therapy.Funding: GlaxoSmithKline; Novartis; National Health and Medical Research Council, Australia; and Melanoma Institute Australia. [ABSTRACT FROM AUTHOR]

Calculating an accurate prognosis for melanoma patients who have a positive sentinel node (SN) biopsy is important both for them and for their treating doctors to guide decision-making, particularly when adjuvant systemic therapy is being considered. The recently published EORTC-DeCOG nomograms aim to provide this via an online portal that predicts 5-year rates for recurrence, distant metastasis and overall mortality. The present study provides external validation of these nomograms. De-identified data from patients with a positive SN biopsy between 2003 and 2015 were extracted from the prospectively maintained Melanoma Institute Australia (MIA) research database. ROC-curves with C-statistics, regression co-efficients and Decision Curve Net Benefit analyses were performed using the integrated private validation portal on the nomograms' hosting platform (Evidencio). Complete data were available for 352 patients. The respective C-statistics for recurrence, distant metastasis and overall mortality nomogram validations were 0.68, 0.69 and 0.66. The performance of the nomograms in predicting recurrence and distant metastasis was similar in the MIA and the development populations, suggesting that they are robust. However, the overall mortality nomogram performance was significantly poorer in the MIA population (C-statistic 0.66) than in the original EORTC-DeCOG derivation cohort (C-statistic 0.70) and may therefore be less reliable for clinical use. • Predicting outcomes for sentinel node-positive melanoma patients is important. • A recently published EORTC-DeCOG online nomogram estimates their prognosis. • This nomogram was externally validated in an Australian population. • The recurrence and distant metastasis prediction models were found to be robust. • The overall survival prediction model was less reliable for Australian patients. [ABSTRACT FROM AUTHOR]

Background: Reduced-dose nivolumab in combination with standard-dose ipilimumab improves objective response and progression-free survival compared with standard-dose ipilimumab alone, but increases toxicity. We assessed the safety and anti-tumour activity of standard-dose pembrolizumab in combination with reduced-dose ipilimumab.Methods: In this open-label, phase 1b trial, we recruited patients from 12 medical centres in Australia, New Zealand, and the USA. Eligible patients were aged at least 18 years, had advanced melanoma, had an Eastern Coooperative Oncology Group performance status of 0 or 1, had measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, had adequate organ function, had resolution of toxic effects of the most recent previous chemotherapy to grade 1 or less, had no active autoimmune disease requiring systemic steroids or immunosuppressive agents, had no active non-infectious pneumonitis, had no uncontrolled thyroid dysfunction or diabetes, had no active brain metastases, and had not received previous immune checkpoint inhibitor therapy. Patients received intravenous pembrolizumab 2 mg/kg plus intravenous ipilimumab 1 mg/kg every 3 weeks for four doses, followed by intravenous pembrolizumab 2 mg/kg every 3 weeks for up to 2 years or disease progression, intolerable toxicity, withdrawal of consent, or investigator decision. The primary endpoint was safety and tolerability. The proportion of patients achieving an objective response assessed per RECIST version 1.1 by independent central review and overall survival were secondary endpoints. We also assessed progression-free survival. The primary endpoint was assessed in all patients who received at least one dose of combination therapy. Activity was assessed in all enrolled patients. This trial is registered with ClinicalTrials.gov, number NCT02089685. Enrolment into this cohort is closed, but patients are still being monitored for safety and anti-tumour activity.Findings: Between Jan 13, 2015, and Sept 17, 2015, we enrolled and treated 153 patients. As of the Oct 17, 2016, cutoff date, median follow-up was 17·0 months (IQR 14·8-18·8). 110 (72%) of 153 patients received all four pembrolizumab plus ipilimumab doses; 64 (42%) remained on pembrolizumab monotherapy. 110 grade 3-4 treatment-related adverse events occurred in 69 (45%) patients. No treatment-related deaths occurred. Treatment-related adverse events led to discontinuation of pembrolizumab and ipilimumab in 22 (14%) patients, including 17 (11%) who discontinued both treatments for the same event and five (3%) who discontinued ipilimumab for one event and later discontinued pembrolizumab for another. 12 (8%) patients discontinued ipilimumab only and 14 (9%) discontinued pembrolizumab only because of treatment-related adverse events. 158 immune-mediated adverse events of any grade occurred in 92 (60%) patients, and 50 immune-mediated adverse events of grade 3-4 occurred in 42 (27%) patients; the most common immune-mediated adverse events were hypothyroidism (25 [16%]) and hyperthyroidism (17 [11%]). 93 (61% [95% CI 53-69]) patients achieved an objective response. Estimated 1 year progression-free survival was 69% (95% CI 60-75), and estimated 1 year overall survival was 89% (95% CI 83-93).Interpretation: Standard-dose pembrolizumab given in combination with four doses of reduced-dose ipilimumab followed by standard-dose pembrolizumab has a manageable toxicity profile and provides robust anti-tumour activity in patients with advanced melanoma. These data suggest that standard-dose pembrolizumab plus reduced-dose ipilimumab might be a tolerable, efficacious treatment option for patients with advanced melanoma. A randomised phase 2 trial of alternative dosing strategies of this combination is underway.Funding: Merck & Co, Inc. [ABSTRACT FROM AUTHOR]

The majority of Merkel cell carcinomas (MCCs) are associated with the recently identified Merkel cell polyomavirus (MCV). However, as it is still unclear to which extent the presence of MCV impacts tumor characteristics or clinical outcome, we correlated the MCV status of tumor lesions obtained from 174 MCC patients including 38 MCC patients from Australia and 138 MCC patients from Germany with clinical characteristics, histomorphology, immunohistochemistry, and course of the disease. MCV DNA was present in 86% of MCCs and, in contrast to previous reports, no significant difference in MCV prevalence was present between Australian and German MCC cases. When patients were stratified according to their MCV status, only tumor localization (P=0.001), gender (P=0.024), and co-morbidity, i.e., frequency of patients with previous skin tumors (P=0.024), were significantly different factors. In contrast, year of birth and diagnosis, age at diagnosis, or histological type and features representing the oncogenic phenotype such as mitotic rate or expression of p16, p53, RB1, and Ki67 were not significantly different between MCV-positive and MCV-negative MCCs. MCV status also did not influence recurrence-free, overall, and MCC-specific survival significantly. In summary, although MCV-positive and MCV-negative MCCs may have different etiologies, these tumors have comparable clinical behaviors and prognosis. [ABSTRACT FROM AUTHOR]

• 50 years of no-till + stubble retention increased soil water, yield and gross margin. • N addition was required for wheat to fully capitalise on increased soil water. • Growing nematode-tolerant cultivars maximised yield response to soil water and N. No-tillage (NT) has been widely adopted to assist in reducing soil erosion, lowering fuel costs, conserving soil water and promoting soil health. However, NT may also have a negative effect on yield depending on season and conditions due to inadequate weed/disease control, nutrient stratification and/or decreased soil temperatures. Therefore, to fully assess its impact, long-term studies are required to monitor changes over time. This study reports on the long-term effect of NT on crop yield and profitability (primarily for wheat, Triticum aestivum L.) using results from an experiment that has been running for 50 years in a semiarid subtropical region of Australia. In this experiment, the effect of tillage (conventional till (CT) v no-till (NT)), residue management (stubble burning (SB) v stubble retention (SR)), and three rates of nitrogen (N) fertiliser (0, 30 and 90 kg N/ha) were measured in a balanced factorial experiment on a Vertisol (Ustic Pellusert). Over the period of the trial (1969–2018), NT with SR resulted in greater average soil water storage in the top 1.5 m of the profile than CT with SB (390 v 346 mm). However, nitrate (NO 3 -N) accumulation during the fallow period was generally lower with SR and this prevented wheat from fully capitalising of on the increased soil water storage. Consequently, while crop yield was greater under NT v CT and more so under NT + SR v CT + SR (particularly in years where in-crop rainfall was <˜300 mm), N fertiliser was required to maximise yields. Within the NT treatments, SR also resulted in greater yield in the presence of applied N. Prior to 1992, nematodes prevented wheat crops from capitalising on the increased soil water and reduced yields, however, the introduction of nematode-tolerant cultivars helped maximise crop production. In line with yield effects, gross margins were greater under NT than CT and for SR when N was applied. However, despite greater yield advantages for the 90 N treatments, gross margins were lower at 90 N compared to 30 N. Nitrogen use efficiency with 90 N was approximately half that with 30 N, likely due to greater losses of N at the higher rates of application. To maximise profitability techniques to reduce losses of N are thus desirable. Good disease control, or the use of tolerant/resistant cultivars, is also essential to allow the crop to capitalise on gains in soil water in NT systems. [ABSTRACT FROM AUTHOR]