Sir Peter MacCallum Department of Oncology - Research Publications

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    Detection of clinically relevant early genomic lesions in B-cell malignancies from circulating tumour DNA using a single hybridisation-based next generation sequencing assay
    Blombery, PA ; Ryland, GL ; Markham, J ; Guinto, J ; Wall, M ; McBean, M ; Jones, K ; Thompson, ER ; Cameron, DL ; Papenfuss, AT ; Prince, MH ; Dickinson, M ; Westerman, DA (WILEY, 2018-10)
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    Characterization of a novel venetoclax resistance mutation (BCL2 Phe104Ile) observed in follicular lymphoma
    Blombery, P ; Birkinshaw, RW ; Nguyen, T ; Gong, J-N ; Thompson, ER ; Xu, Z ; Westerman, DA ; Czabotar, PE ; Dickinson, M ; Huang, DCS ; Seymour, JF ; Roberts, AW (WILEY, 2019-09)
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    A multicentre retrospective comparison of central nervous system prophylaxis strategies among patients with high-risk diffuse large B-cell lymphoma
    Cheah, CY ; Herbert, KE ; O'Rourke, K ; Kennedy, GA ; George, A ; Fedele, PL ; Gilbertson, M ; Tan, SY ; Ritchie, DS ; Opat, SS ; Prince, HM ; Dickinson, M ; Burbury, K ; Wolf, M ; Januszewicz, EH ; Tam, CS ; Westerman, DA ; Carney, DA ; Harrison, SJ ; Seymour, JF (NATURE PUBLISHING GROUP, 2014-09-09)
    BACKGROUND: Central nervous system (CNS) relapse in diffuse large B-cell lymphoma (DLBCL) is a devastating complication; the optimal prophylactic strategy remains unclear. METHODS: We performed a multicentre, retrospective analysis of patients with DLBCL with high risk for CNS relapse as defined by two or more of: multiple extranodal sites, elevated serum LDH and B symptoms or involvement of specific high-risk anatomical sites. We compared three different strategies of CNS-directed therapy: intrathecal (IT) methotrexate (MTX) with (R)-CHOP 'group 1'; R-CHOP with IT MTX and two cycles of high-dose intravenous (IV) MTX 'group 2'; dose-intensive systemic antimetabolite-containing chemotherapy (Hyper-CVAD or CODOXM/IVAC) with IT/IV MTX 'group 3'. RESULTS: Overall, 217 patients were identified (49, 125 and 43 in groups 1-3, respectively). With median follow-up of 3.4 (range 0.2-18.6) years, 23 CNS relapses occurred (12, 10 and 1 in groups 1-3 respectively). The 3-year actuarial rates (95% CI) of CNS relapse were 18.4% (9.5-33.1%), 6.9% (3.5-13.4%) and 2.3% (0.4-15.4%) in groups 1-3, respectively (P=0.009). CONCLUSIONS: The addition of high-dose IV MTX and/or cytarabine was associated with lower incidence of CNS relapse compared with IT chemotherapy alone. However, these data are limited by their retrospective nature and warrant confirmation in prospective randomised studies.
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    Limited clinical benefit for surveillance PET-CT scanning in patients with histologically transformed lymphoma in complete metabolic remission following primary therapy
    Cheah, CY ; Dickinson, M ; Hofman, MS ; George, A ; Ritchie, DS ; Prince, HM ; Westerman, D ; Harrison, SJ ; Burbury, K ; Wolf, M ; Januszewicz, H ; Herbert, KE ; Carney, DA ; Tam, C ; Seymour, JF (SPRINGER, 2014-07)
    The optimum follow-up of patients with transformed indolent lymphoma (TrIL) is not well defined. We sought to determine the utility of surveillance positron emission tomography-computed tomography (PET-CT) in patients with TrIL achieving complete metabolic remission (CMR) after primary therapy. We performed a retrospective analysis of patients with TrIL treated at Peter MacCallum Cancer Centre between 2002 and 2012 who achieved CMR after primary therapy who had ≥1 subsequent surveillance PET-CT. Of 55 patients with TrIL, 37 (67 %) received autologous stem cell transplantation as consolidation following chemoimmunotherapy. After a median follow-up of 34 (range 3-101) months, the actuarial 3-year progression-free (PFS) and overall survival (OS) were 77 % (95 %CI 62-86 %) and 88 % (75-94 %), respectively. Of 180 surveillance PET-CT scans, there were 153 true negatives, 4 false positives, 1 false negative, 7 indeterminate and 15 true positives. Considering indeterminate scans as false positives, the specificity of PET-CT for detecting relapse was 94 %, sensitivity was 83 %, positive predictive value was 63 % and negative predictive value was 98 %. All seven subclinical (PET detected) relapses were of low-grade histology; in contrast, all nine relapses with diffuse large B cell lymphoma (DLBCL) were symptomatic. In our cohort of patients with TrIL achieving CMR, PET-CT detected subclinical low-grade relapses but all DLBCL relapses were accompanied by clinical symptoms. Thus, surveillance imaging of patients with TrIL achieving CMR is of limited clinical benefit. PET-CT should be reserved for evaluation of clinically suspected relapse.
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    Limited role for surveillance PET-CT scanning in patients with diffuse large B-cell lymphoma in complete metabolic remission following primary therapy
    Cheah, CY ; Hofman, MS ; Dickinson, M ; Wirth, A ; Westerman, D ; Harrison, SJ ; Burbury, K ; Wolf, M ; Januszewicz, H ; Herbert, K ; Prince, HM ; Carney, DA ; Ritchie, DS ; Hicks, RJ ; Seymour, JF (NATURE PUBLISHING GROUP, 2013-07-23)
    BACKGROUND: The usefulness of positron emission tomography with computed tomography (PET-CT) in the surveillance of patients with diffuse large B-cell lymphoma (DLBCL) in complete metabolic remission after primary therapy is not well studied. METHODS: We performed a retrospective review of our database between 2002 and 2009 for patients with de novo DLBCL who underwent surveillance PET-CT after achieving complete metabolic response (CMR) following primary therapy. RESULTS: Four-hundred and fifty scans were performed in 116 patients, with a median follow-up of 53 (range 8-133) months from completion of therapy. Thirteen patients (11%) relapsed: seven were suspected clinically and six were subclinical (all within first 18 months). The positive predictive value in patients with international prognostic index (IPI) <3 was 56% compared with 80% in patients with IPI ≥3. Including indeterminate scans, PET-CT retained high sensitivity 95% and specificity 97% for relapse. CONCLUSION: Positron emission tomography with computed tomography is not useful in patients for the majority of patients with diffuse large B-cell lymphoma in CMR after primary therapy, with the possible exception of patients with baseline IPI ≥3 in the 18 months following completion of primary therapy. This issue could be addressed by a prospective clinical trial.