Medical oncologist perceptions and willingness to participate in voluntary assisted dying in South Australia.

This study surveyed South Australian medical oncologists to capture their perceptions, willingness to participate and perceived barriers and motivations to participation in voluntary assisted dying (VAD) activities. Approximately 70% of surveyed medical oncologists reported familiarity with VAD legislation. Less than half of physicians (39.1%) reported willingness to participate in any VAD activities, and the rate of conscientious objection was 22%. The top barriers to participation were lack of time and uncertainty given no prior experience. These results demonstrate both a low rate of conscientious objection and a low rate of willingness to participate at the point of VAD implementation in South Australia, and identify barriers to participation that are largely logistical.

Asciminib is a novel inhibitor of ABL1 and ABL2 gene fusions in ALL but requires the ABL SH3 domain for efficacy.

High-risk Ph-like ALL includes genomic rearrangement of the ABL1 and ABL2 genes (collectively ABL-rearranged, ABLr), and novel treatments are required. For the first time, we demonstrate asciminib efficacy in ABLr ALL, but only when the ABL SH3 domain is present.

TP53 loss­of­function mutations reduce sensitivity of acute leukaemia to the curaxin CBL0137.

The presence of a TP53 mutation is a predictor of poor outcome in leukaemia, and efficacious targeted therapies for these patients are lacking. The curaxin CBL0137 has demonstrated promising antitumour activities in multiple cancers such as glioblastoma, acting through p53 activation, NF­κB inhibition and chromatin remodelling. In the present study, it was revealed using Annexin­V/7­AAD apoptosis assays that CBL0137 has efficacy across several human acute leukaemia cell lines with wild­type TP53, but sensitivity is reduced in TP53­mutated subtypes. A heterozygous TP53 loss­of­function mutation in the KMT2A­AFF1 human RS4;11 cell line was generated, and it was demonstrated that heterozygous TP53 loss­of­function is sufficient to cause a significant reduction in CBL0137 sensitivity. To the best of our knowledge, this is the first evidence to suggest a clinically significant role for functional p53 in the efficacy of CBL0137 in acute leukaemia. Future CBL0137 clinical trials should include TP53 mutation screening, to establish the clinical relevance of TP53 mutations in CBL0137 efficacy.

MLLT10 rearranged acute leukemia: Incidence, prognosis, and possible therapeutic strategies.

Rearrangements of the MLLT10 gene occur in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), most commonly T-lineage ALL (T-ALL), in patients of all ages. MLLT10 rearranged (MLLT10r) acute leukemia presents a complex diagnostic and therapeutic challenge due to frequent presentation of immature or mixed phenotype, and a lack of consensus regarding optimal therapy. Cases of MLLT10r AML or T-ALL bearing immature phenotype are at high risk of poor outcome, but the underlying molecular mechanisms and sensitivity to targeted therapies remain poorly characterized. This review addresses the incidence and prognostic significance of MLLT10r in acute leukemia, and how the aberrant gene expression profile of this disease can inform potential targeted therapeutic strategies. Understanding the underlying genomics of MLLT10r acute leukemia, both clinically and molecularly, will improve prognostic stratification and accelerate the development of targeted therapeutic strategies, to improve patient outcomes.

KMT2A rearranged acute lymphoblastic leukaemia: Unravelling the genomic complexity and heterogeneity of this high-risk disease.

KMT2A rearranged (KMT2Ar) acute lymphoblastic leukaemia (ALL) is a high-risk genomic subtype, with long-term survival rates of less than 60% across all age groups. These cases present a complex clinical challenge, with a high incidence in infants, high-risk clinical features and propensity for aggressive relapse. KMT2A rearrangements are highly pathogenic leukaemic drivers, reflected by the high incidence of KMT2Ar ALL in infants, who carry few leukaemia-associated cooperative mutations. However, transgenic murine models of KMT2Ar ALL typically exhibit long latency and mature or mixed phenotype, and fail to recapitulate the aggressive disease observed clinically. Next-generation sequencing has revealed that KMT2Ar ALL also occurs in adolescents and adults, and potentially cooperative genomic lesions such as PI3K-RAS pathway variants are present in KMT2Ar patients of all ages. This review addresses the aetiology of KMT2Ar ALL, with a focus on the cell of origin and mutational landscape, and how genomic profiling of KMT2Ar ALL patients in the era of next-generation sequencing demonstrates that KMT2Ar ALL is a complex heterogenous disease. Ultimately, understanding the underlying biology of KMT2Ar ALL will be important in improving long-term outcomes for these high-risk patients.

Satisfaction with care in men with prostate cancer.

PURPOSE: This study aims to describe: (a) the proportion of prostate cancer patients satisfied with treatment, (b) how satisfaction changes after treatment, and (c) predictors of patient satisfaction including demographic, symptom-related and treatment variables. METHOD: Self-reported quality of life and satisfaction questionnaire (UCLA Expanded Prostate Cancer Index Composite [EPIC] 26), and demographics were obtained from the South Australian Prostate Cancer Clinical Outcomes Collaborative (SA-PCCOC) database. Responses were obtained pre-treatment (radical prostatectomy or external beam radiation therapy) and 6, 12 and 24 months post-treatment, for patients diagnosed between 2009 and 2013. Mixed-effects models were used to estimate mean and change in satisfaction, and to identify predictive factors. RESULTS: SA-PCCOC is a prospective, prostate cancer specific registry established in 1998, of which 1,713 patients were eligible for inclusion and 434 available for analysis. Overall, the majority of patients who completed questionnaires were satisfied with their treatment (82%). Satisfaction with care did not change over time post-treatment in multivariable analysis (p = 0.08). CONCLUSIONS: Satisfaction with treatment is typically high among prostate cancer patients. Satisfaction did not change with time after treatment and appears to be associated with baseline hormonal scores and changes in hormonal scores post-treatment.