Medicine (RMH) - Research Publications
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ItemOutcomes of women at high familial risk for breast cancer: An 8-year single-center experience(WILEY, 2020-04)OBJECTIVES: The value of a high-risk surveillance program for mutation carriers and women at high familial breast cancer risk has not been extensively studied. A Breast and Ovarian Cancer Risk Management Clinic (BOCRMC) was established at the Royal Melbourne Hospital in 2010 to provide multimodality screening and risk management strategies for this group of women. The aims of this study were to evaluate the program and describe breast cancer diagnoses for BRCA1, BRCA2, and other germline mutation carriers as well as high-risk noncarriers attending the BOCRMC. METHODS: Clinical data from mutation carriers and noncarriers with a ≥25% lifetime risk of developing breast cancer who attended between 2010 and 2018 were extracted from clinic records and compared. The pattern and mode of detection of cancer were determined. RESULTS: A total of 206 mutation carriers and 305 noncarriers attended the BOCRMC and underwent screening on at least one occasion. Median age was 37 years. After a median follow-up of 34 months, 15 (seven invasive) breast cancers were identified in mutation carriers, with seven (six invasive) breast cancers identified in noncarriers. Of these, 20 (90.9%) were detected by annual screening, whereas two (9.1%) were detected as interval cancers (both in BRCA1 mutation carriers). Median size of the invasive breast cancers was 11 mm (range: 1.5-30 mm). The majority (76.9%) were axillary node negative. In women aged 25-49 years, the annualized cancer incidence was 1.6% in BRCA1, 1.4% in BRCA2 mutation carriers, and 0.5% in noncarriers. This compares to 0.06% annualized cancer incidence in the general Australian population. CONCLUSIONS: Screening was effective at detecting early-stage cancers. The incidence of events in young noncarriers was substantially higher than in the general population. This potentially justifies ongoing management through a specialty clinic, although further research to better personalize risk assessment in noncarriers is required.
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ItemNo Preview AvailableIntegrating Shared Survivorship Care into an Allogeneic Bone Marrow Transplant Long Term Follow up Service(ELSEVIER SCIENCE INC, 2020-03)
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ItemHepatology Clinical(WILEY, 2020-11)
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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.
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ItemA TOOLKIT FOR THE QUANTITATIVE ANALYSIS OF THE SPATIAL DISTRIBUTION OF CELLS OF THE TUMOR IMMUNE MICROENVIRONMENT(BMJ PUBLISHING GROUP, 2020-11)
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Item372. Comparing the Outcome of COVID-19 in Cancer and Non-Cancer Patients: an International Multicenter Study(Oxford University Press (OUP), 2020-12-31)Abstract Background Our objective was to describe the clinical course, risk factors and outcomes of patients infected with COVID-19 around the globe comparing cancer to non-cancer patients. Methods We conducted a retrospective cohort study of COVID-19 confirmed cases through an international multicenter collaboration including 17 centers around the world including the United States of America, Brazil, Europe, Far East, Middle East and Australia from January to date. We evaluated the patients’ clinical characteristics, clinical course of the disease, hospitalization and outcome. Death was considered to be COVID-associated if it occurred within 30 days from the time of diagnosis. Results Preliminary data on 571 patients included 186 cancer patients and 385 non-cancer patients. Cancer patients were more likely to have COPD and received steroids but were less likely to have COVID-related symptoms compared to non-cancer patients (84% vs 97%, p< 0.0001). The rate of pneumonia with hypoxia, non-invasive ventilation and mechanical ventilation were similar in both groups. Despite the fact that hospital admissions were significantly higher in non-cancer patients (70% vs 56%, p< 0.001), promising antiviral and immune-related therapy including remdesivir, convalescent plasma and immunomodulators were more commonly used in cancer patients compared to non-cancer patients (P=0.04). Cancer patients had a higher COVID-associated mortality rate compared to non-cancer patients (20% vs 11%, p=0.006). Conclusion Despite the fact that cancer patients received more frequent antiviral and immune-related therapy, the mortality rate among cancer patients was significantly higher than non-cancer patients. Disclosures Roy F. Chemaly, MD, MPH, FACP, FIDSA, Chimerix (Consultant, Research Grant or Support)Clinigen (Consultant)Merck (Consultant, Research Grant or Support)Novartis (Research Grant or Support)Oxford Immunotec (Consultant, Research Grant or Support)Shire/Takeda (Research Grant or Support)Viracor (Research Grant or Support) Issam I. Raad, MD, Citius (Other Financial or Material Support, Ownership interest)Cook Medical (Grant/Research Support)Inventive Protocol (Other Financial or Material Support, Ownership interest)Novel Anti-Infective Technologies (Shareholder, Other Financial or Material Support, Ownership interest)
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ItemSUN-127 Diagnostic Challenges Associated with the Rising Incidence of Endocrine Toxicity in the Era of Combination Immunotherapy(The Endocrine Society, 2020-05-08)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
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