Sir Peter MacCallum Department of Oncology - Research Publications
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ItemSUBA-Itraconazole for Primary Antifungal Prophylaxis After Allogeneic Hematopoietic Cell Transplantation(OXFORD UNIV PRESS INC, 2021-11-01)Background: Itraconazole (ITZ) is an effective agent when used as primary invasive fungal disease (IFD) prophylaxis, but is limited by drug tolerability and variability in serum concentrations. A new formulation, SUBA-itraconazole (for "super bioavailability"; S-ITZ), addresses the limitations of conventional ITZ formulations. Methods: We conducted a retrospective cohort study at 2 Australian centers to evaluate the safety, tolerability, and effectiveness of S-ITZ as primary antifungal prophylaxis in hematopoietic cell transplant (HCT) recipients without grade II-IV acute graft-vs-host disease, from day 1 until approximately day 100 (cohort A) or day 1 until neutrophil engraftment (cohort B). A total of 204 patients and 1410 trough plasma ITZ concentrations were assessed. Results: The incidence of breakthrough proven/probable IFD at day 180 was 1.0% (95% confidence interval [CI], .2%-3.2%), with 1.6% in cohort A and 0% in cohort B, and overall fungal-free survival of proven/probable IFD was 82.9% (95% CI, 76.8%-87.4%). Preengraftment early permanent S-ITZ discontinuation was 3.4% overall, with no significant difference between cohorts. No patients required cessation due to gastrointestinal intolerance attributed to S-ITZ. The geometric mean trough plasma ITZ concentration was 1130ng/mL (interquartile range, 566-1801ng/mL; coefficient of variation, 56.57%) and the median time to achieve therapeutic levels was 10 days. Conclusions: S-ITZ is a safe and well-tolerated oral formulation and is a novel alternative for primary IFD prophylaxis after HCT.
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ItemImpact of lymphopenia on survival for elderly patients with glioblastoma: A secondary analysis of the CCTG CE.6 (EORTC 26062-22061, TROG03.01) randomized clinical trial.(Oxford University Press (OUP), 2021-01)BACKGROUND: Lymphopenia may lead to worse outcomes for glioblastoma patients. This study is a secondary analysis of the CCTG CE.6 trial evaluating the impact of chemotherapy and radiation on lymphopenia, and effects of lymphopenia on overall survival (OS). METHODS: CCTG CE.6 randomized elderly glioblastoma patients (≥ 65 years) to short-course radiation alone (RT) or short-course radiation with temozolomide (RT + TMZ). Lymphopenia (mild-moderate: grade 1-2; severe: grade 3-4) was defined per CTCAE v3.0, and measured at baseline, 1 week and 4 weeks post-RT. Preselected key factors for analysis included age, sex, ECOG, resection extent, MGMT methylation, Mini-Mental State Examination, and steroid use. Multinomial logistic regression and multivariable Cox regression models were used to identify lymphopenia-associated factors and association with survival. RESULTS: Five hundred and sixty-two patients were analyzed (281 RT vs 281 RT+TMZ). At baseline, both arms had similar rates of mild-moderate (21.4% vs 21.4%) and severe (3.2% vs 2.9%) lymphopenia. However, at 4 weeks post-RT, RT+TMZ was more likely to develop lymphopenia (mild-moderate: 27.9% vs 18.2%; severe: 9.3% vs 1.8%; p<0.001). Developing any lymphopenia post-RT was associated with baseline lymphopenia (P < .001). Baseline lymphopenia (hazard ratio [HR] 1.3) was associated with worse OS (HR: 1.30, 95% confidence interval [CI] 1.05-1.62; P = .02), regardless of MGMT status. CONCLUSIONS: Development of post-RT lymphopenia is associated with addition of TMZ and baseline lymphopenia and not with RT alone in patients treated with short-course radiation. However, regardless of MGMT status, only baseline lymphopenia is associated with worse OS, which may be considered as a prognostic biomarker for elderly glioblastoma patients.
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ItemTissue-specific tumour microenvironments are an emerging determinant of immunotherapy responses(AME PUBL CO, 2020-08-01)
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ItemChallenges of PD-L1 testing in non-small cell lung cancer and beyond(AME PUBL CO, 2020-08-01)
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ItemGelfoam slurry tract occlusion after computed tomography-guided percutaneous lung biopsy: Does it prevent major pneumothorax?(WILEY, 2021-06-13)INTRODUCTION: Computed tomography (CT)-guided lung biopsy is a frequently performed procedure in the diagnostic workup for suspicious lung nodules that can be complicated by pneumothorax. This retrospective study assessed the efficacy of biopsy tract occlusion with a gelatin sponge slurry for preventing post-biopsy pneumothorax. METHODS: Retrospective analysis was conducted on consecutive adult patients who underwent CT-guided lung biopsy over a 10-year period. Age, gender, existing chronic obstructive pulmonary disease (COPD), evidence of emphysema on CT, location of the lesion and the presence of pneumothorax on post-procedure CT and 4-h chest radiograph were recorded. RESULTS: Two hundred and ninety-six patients were included (126 patients in the non-gelfoam group and 170 in the gelfoam group). When gelfoam was used, risk of developing an immediate pneumothorax was lower (P = 0.032). Patients with emphysema were 2.4 times more likely to develop a delayed pneumothorax without gelfoam (P = 0.034). There was a significantly higher risk of both immediate and delayed pneumothorax in non-peripheral lesions without gelfoam (P = 0.001 and P = 0.002, respectively). The frequency of requiring a chest tube to treat a pneumothorax was 86% lower when gelfoam was used (P = 0.012). CONCLUSION: Gelfoam is effective in preventing immediate pneumothorax. In patients with emphysema, there was a significantly higher risk of delayed pneumothorax without gelfoam. Additionally, non-peripheral lesions were more likely to develop pneumothorax when gelfoam was not used. The use of gelfoam was especially important in preventing the development of major pneumothoraces that would require drainage with a chest tube.
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ItemGlial Hedgehog signalling and lipid metabolism regulate neural stem cell proliferation in Drosophila(WILEY, 2021-03-10)The final size and function of the adult central nervous system (CNS) are determined by neuronal lineages generated by neural stem cells (NSCs) in the developing brain. In Drosophila, NSCs called neuroblasts (NBs) reside within a specialised microenvironment called the glial niche. Here, we explore non-autonomous glial regulation of NB proliferation. We show that lipid droplets (LDs) which reside within the glial niche are closely associated with the signalling molecule Hedgehog (Hh). Under physiological conditions, cortex glial Hh is autonomously required to sustain niche chamber formation. Upon FGF-mediated cortex glial overgrowth, glial Hh non-autonomously activates Hh signalling in the NBs, which in turn disrupts NB cell cycle progression and its ability to produce neurons. Glial Hh's ability to signal to NB is further modulated by lipid storage regulator lipid storage droplet-2 (Lsd-2) and de novo lipogenesis gene fatty acid synthase 1 (Fasn1). Together, our data suggest that glial-derived Hh modified by lipid metabolism mechanisms can affect the neighbouring NB's ability to proliferate and produce neurons.
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ItemNo Preview AvailablePredicting Malignancy in FDG-avid Thyroid Nodules based on Standardized Uptake Value in Oncology Patients(Jaypee Brothers Medical Publishing, 2021-03-01)
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ItemNo Preview AvailableIndications for definitive chemoradiotherapy for oesophageal cancer(AME Publishing Company, 2021-12-01)Oesophageal cancer is the ninth most common cancer diagnosed, and seventh most common cause of cancer-related deaths worldwide. Despite significant advances in imaging, surgery, radiotherapy and systemic therapy over the past few decades, treatment outcomes in patients with localised oesophageal cancer remain suboptimal with a 5-year overall survival of less than 50%. Current treatment guidelines recommend surgery with/without pre-operative chemotherapy or chemoradiotherapy for patients with localised resectable disease. Hence, definitive radiotherapy (with or without chemotherapy) has predominantly been reserved for those who are deemed unsuitable for surgery. The role of radiotherapy in definitive management of oesophageal cancer has been recognised since the 1960s. The addition of concurrent chemotherapy has shown to improve treatment outcomes and has remained standard of care since the RTOG 85-01 and Intergroup 0123 trials. This review discusses the current literature on definitive radiotherapy with/without chemotherapy for localised oesophageal cancer, and evaluates current radiation modalities and technological developments in radiotherapy planning and delivery. We will provide an overview on the literature for definitive chemoradiotherapy in oesophageal cancer, the epidemiological and treatment response differences between squamous cell carcinoma and adenocarcinoma of the oesophagus, followed by a review of the current literature on different radiation treatment modalities (intensity modulated radiotherapy, brachytherapy and proton therapy) and the use of different imaging modalities for radiation treatment planning.