Medicine (St Vincent's) - Research Publications
Permanent URI for this collection
Search Results
1 - 10 of 17
-
ItemOR32-06 Opportunistic Assessment of Pituitary Gland with Routine MRI and PET/CT Can Guide in Earlier and Increased Identification of Hypophysitis in Patients Treated with Combination Checkpoint Inhibitors( 2020-05)Abstract Background: Hypophysitis is one of the commonly reported adverse events related to immune checkpoint inhibitors (ICI), and the incidence is expected to rise with increased use of combined programmed cell death protein 1 (PD1) and cytotoxic T lymphocyte associated protein 4 (CTLA4) blockade. The clinical diagnosis can be delayed due to non-specific symptoms. At our centre, subjects undergo periodic imaging to assess tumour response to ICI. We reviewed whether neuroimaging studies can guide us in the diagnosis of hypophysitis and whether early changes can be detected before the onset of the clinical syndrome. Methods: We retrospectively reviewed the medical charts, biochemistry, structural brain imaging and whole-body positron emission tomography (PET) with specific reference to hypophysitis in 162 patients treated with combination ICI at a tertiary melanoma referral centre. Suspected cases were identified based on meeting one or more of the following criteria: 1) A documented diagnosis of hypophysitis or pituitary dysfunction found on chart review, 2) A relative change in pituitary size or appearance from baseline on neuroimaging studies, or 3) An increase in pituitary maximum standardized uptake value (SUVmax) greater than 25% from baseline on 18F-FDG PET. Results: 58/162 patients (36%) met criteria for suspected hypophysitis. Only 4 patients were identified on routine screening of early morning cortisol. 14 patients presented with symptoms leading to biochemical work up. A further 40 patients were found to have suspicious imaging changes, 13 of which went on to receive a formal diagnosis of hypophysitis. Of the remaining 27 patients, 23 were receiving high dose glucocorticoids for concomitant immune related adverse events at the time of the abnormal imaging study.Conclusion: We report the highest incidence to date of suspected hypophysitis in cohort of patients treated with combination ICI. This study highlights the important role of structural and functional neuroimaging in the early recognition of hypophysitis. Imaging may also play a role when the clinical syndrome is masked by concurrent glucocorticoid use.
-
ItemSUN-127 Diagnostic Challenges Associated with the Rising Incidence of Endocrine Toxicity in the Era of Combination Immunotherapy( 2020-05)Abstract Background: Immune checkpoint blockade is now established as standard of care in several malignancies. Trials involving combined cytotoxic T lymphocyte associated protein 4 (CTLA4) and programmed cell death protein 1 (PD1) blockade demonstrate improved tumour responses in melanoma but at the cost of severe grade 3-4 immune related adverse events (irAEs) in 55%, and endocrine irAEs in up to 10% [1]. Immune-mediated damage to endocrine glands can be a diagnostic and management challenge. We aimed to review the incidence, biochemical evolution and imaging findings of endocrine toxicity related to combined anti CTLA-4 and anti-PD-1 therapy. Methods: We undertook a retrospective chart review of patients who received combined ipilimumab and nivolumab for metastatic melanoma at a tertiary referral centre between 2016-2019. We recorded onset and duration of abnormal biochemistry in endocrine irAEs, reviewed all available MRI images for pituitary size (mm) and appearance and 18-F FDG PET images for features of hypophysitis, thyroiditis and pancreatitis. Results: 162 patients received combination therapy. At least one irAE was recorded in 135 patients (83%), 100 (62%) required glucocorticoids, and 84 (52%) had an unplanned hospital presentation due to irAEs. Thyroiditis occurred in 50 (30.9%), with median time to onset of 30.9 days (range 1-234 days). 35 cases were identified with routine biochemistry performed every 4-6 weeks. TSH receptor antibody was measured in 13 patients and all were negative. 29 (58%) developed permanent hypothyroidism. Central cortisol deficiency was documented in 31 (19%) with a median time to diagnosis of 67.5 days (range 5-286). 4 cases were diagnosed on routine biochemistry and 14 presented with symptoms prompting investigation. 13 were diagnosed after routine neuroimaging demonstrated a pituitary abnormality, and a further 27 patients without the clinical syndrome had features of hypophysitis on neuroimaging. New onset diabetes occurred in 3 people, in which pancreatic inflammation on imaging was found in 2. A further 3/5 patients with an asymptomatic elevated lipase were found to have abnormal pancreatic imaging. In one patient with no features of endocrine or exocrine failure, there was a significant increase in FDG uptake and a subsequent loss of pancreatic volume. Conclusion: We report real world incidence of endocrine irAEs with combination immunotherapy. Routine biochemistry leads to the detection of some but not all cases. Early recognition and avoidance of unplanned presentations remains a challenge. Opportunistic assessment of endocrine gland appearance on routine imaging studies may provide useful early diagnostic information. Reference: Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. (2015) 1:23-34. 10.1056/NEJMoa1504030
-
ItemNo Preview AvailableOR32-06 Opportunistic Assessment of Pituitary Gland with Routine MRI and PET/CT Can Guide in Earlier and Increased Identification of Hypophysitis in Patients Treated with Combination Checkpoint Inhibitors(The Endocrine Society, 2020-05-08)Abstract Background: Hypophysitis is one of the commonly reported adverse events related to immune checkpoint inhibitors (ICI), and the incidence is expected to rise with increased use of combined programmed cell death protein 1 (PD1) and cytotoxic T lymphocyte associated protein 4 (CTLA4) blockade. The clinical diagnosis can be delayed due to non-specific symptoms. At our centre, subjects undergo periodic imaging to assess tumour response to ICI. We reviewed whether neuroimaging studies can guide us in the diagnosis of hypophysitis and whether early changes can be detected before the onset of the clinical syndrome. Methods: We retrospectively reviewed the medical charts, biochemistry, structural brain imaging and whole-body positron emission tomography (PET) with specific reference to hypophysitis in 162 patients treated with combination ICI at a tertiary melanoma referral centre. Suspected cases were identified based on meeting one or more of the following criteria: 1) A documented diagnosis of hypophysitis or pituitary dysfunction found on chart review, 2) A relative change in pituitary size or appearance from baseline on neuroimaging studies, or 3) An increase in pituitary maximum standardized uptake value (SUVmax) greater than 25% from baseline on 18F-FDG PET. Results: 58/162 patients (36%) met criteria for suspected hypophysitis. Only 4 patients were identified on routine screening of early morning cortisol. 14 patients presented with symptoms leading to biochemical work up. A further 40 patients were found to have suspicious imaging changes, 13 of which went on to receive a formal diagnosis of hypophysitis. Of the remaining 27 patients, 23 were receiving high dose glucocorticoids for concomitant immune related adverse events at the time of the abnormal imaging study.Conclusion: We report the highest incidence to date of suspected hypophysitis in cohort of patients treated with combination ICI. This study highlights the important role of structural and functional neuroimaging in the early recognition of hypophysitis. Imaging may also play a role when the clinical syndrome is masked by concurrent glucocorticoid use.
-
ItemPhase 2 Study of Cemiplimab in Patients with Advanced Cutaneous Squamous Cell Carcinoma (CSCC): Longer Follow-Up(National Society for Cutaneous Medicine, 2020-10-27)Abstract not available.
-
ItemCemiplimab Improves Health-Related Quality of Life (HRQoL) and Reduces Pain in Patients with Advanced Cutaneous Squamous Cell Carcinoma (CSCC): Results from a Post Hoc Exploratory Analysis of a Phase 2 Clinical Trial(National Society for Cutaneous Medicine, 2021-01-01)Abstract not available.
-
ItemNo Preview AvailableChallenges in data linkage - experiences from an upper gastrointestinal cancer data linkage study(OXFORD UNIV PRESS, 2021-09)Abstract Background Linked, population-level data is valuable for mapping patterns of care and evaluating health service utilisation, particularly in difficult-to-reach populations. Upper gastrointestinal (UGI) cancers have a dismal prognosis, creating difficulties engaging patients in research. The utility of a linked dataset in this population is of high value. Methods Key objectives included identifying the operational and feasibility issues associated with linking Australian state-based administrative and registry data for understanding health service utilisation in UGI cancers. Datasets pertained to hospital admissions, radiotherapy, community health, primary care, palliative care, Medicare and Pharmaceutical Benefits Schedule’s and UGI cancers. Results From a logistical perspective, data access request approval processes varied, with some requiring consent to be sought from individual services contributing data. The availability of unique person-level identifying information varied widely. Additionally, the time period of data capture differed between and within datasets, limiting the quality of the linked data. Significant costs were associated with linking with primary care and Medicare and Pharmaceutical Benefits Schedule’s. Federal dataset linkage required at least a one-year waiting period. Conclusions Whilst in theory data linkage is a powerful mechanism for obtaining population-level data, in reality, there are many logistical and financial barriers to linking multiple datasets. Consequently, critical data, which has the potential to inform policy and improve patient outcomes, cannot be procured. Key messages Logistical and financial challenges are associated with linking administrative and registry datasets for research, limiting the potential of data linkage.
-
ItemNo Preview Available
-
ItemA PHASE II STUDY OF CONTINUOUS LOW DOSE PANOBINOSTAT IN PAEDIATRIC PATIENTS WITH MALIGNANT RHABDOID TUMORS/ATYPICAL TERATOID RHABDOID TUMORS(OXFORD UNIV PRESS INC, 2020-12)Abstract
BACKGROUND
Panobinostat treatment has been shown to terminally differentiate malignant rhabdoid tumor (MRT)/atypical teratoid rhabdoid tumors (ATRT) in pre-clinical models. This is an open label, phase II study of panobinostat in patients with newly diagnosed or relapsed MRT/ATRT. AIMS: To assess the anti-tumor activity of low dose, continuous panobinostat, its associated toxicities, the biological activity of low dose panobinostat by measuring histone acetylation status in peripheral mononuclear cells (PMNC), and markers of differentiation in fresh tumor tissue specimens.METHODS
Following cycles of induction and consolidation chemotherapy and/or radiation treatment, patients were enrolled and commenced on panobinostat as a continuous daily oral dose starting at 10mg/m2 following a three-week wash out period between therapies. Real-time acetylation status, measuring acetylated H4 on PMNC, was performed to determine the pharmacodynamics of panobinostat. Patients were monitored for drug toxicities with the possibility of dose reductions in decrements of 2mg/m2.RESULTS
Six patients with newly diagnosed ATRT/MRT and one patient with relapsed MRT have been enrolled to date. The average age at enrollment was 2.5 years. Currently, six patients (85.7%) remain on study with a mean treatment duration of 170 days (range 44–327 days). One patient was removed from study at day 44 due to disease progression. The main dose-limiting toxicity observed to date has been myelosuppression. Panobinostat, at a dose of 10mg/m2, caused significant acetylation of H4 in PMNC.CONCLUSIONS
Treatment with panobinostat appears to be well tolerated in infants with MRT/ATRT, with successful real-time pharmacodynamic assessment of H4 acetylation. -
Item
-
ItemAutologous stem cell transplantation for untreated transformed indolent B-cell lymphoma in first remission: an international, multi-centre propensity-score-matched study(WILEY, 2020-12)High-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) are used as consolidation in first remission (CR1) in some centres for untreated, transformed indolent B-cell lymphoma (Tr-iNHL) but the evidence base is weak. A total of 319 patients with untreated Tr-iNHL meeting prespecified transplant eligibility criteria [age <75, LVEF ≥45%, no severe lung disease, CR by positron emission tomography or computed tomography ≥3 months after at least standard cyclophosphamide, doxorubicin, vincristine and prednisolone with rituximab (R-CHOP) intensity front-line chemotherapy] were retrospectively identified. Non-diffuse large B-cell lymphoma transformations were excluded. About 283 (89%) patients had follicular lymphoma, 30 (9%) marginal-zone lymphoma and six (2%) other subtypes. Forty-nine patients underwent HDC/ASCT in CR1, and a 1:2 propensity-score-matched cohort of 98 patients based on age, stage and high-grade B-cell lymphoma with MYC, BCL2 and/or BCL6 rearrangements (HGBL-DH) was generated. After a median follow-up of 3·7 (range 0·1-18·3) years, ASCT was associated with significantly superior progression-free survival [hazard ratio (HR) 0·51, 0·27-0·98; P = 0·043] with a trend towards inferior overall survival (OS; HR 2·36;0·87-6·42; P = 0·1) due to more deaths from progressive disease (8% vs. 4%). Forty (41%) patients experienced relapse in the non-ASCT cohort - 15 underwent HDC/ASCT with seven (47%) ongoing complete remission (CR); 10 chimeric antigen receptor-modified T-cell (CAR-T) therapy with 6 (60%) ongoing CR; 3 allogeneic SCT with 2 (67%) ongoing CR. Although ASCT in CR1 improves initial duration of disease control in untreated Tr-iNHL, the impact on OS is less clear with effective salvage therapies in this era of CAR-T.