Eliza Hawkes

A multicenter retrospective comparison of induction chemoimmunotherapy regimens on outcomes in transplant-eligible patients with previously untreated mantle cell lymphoma.

Publisher: Wiley

Date: 24-05-2019

DOI: 10.1002/HON.2618

Abstract: Mantle cell lymphoma (MCL) is an uncommon and typically aggressive form of lymphoma. Although often initially chemosensitive, relapse is common. Several induction and conditioning regimens are used in transplant-eligible patients, and the optimal approach remains unknown. We performed an international, retrospective study of transplant-eligible patients to assess impact of induction chemoimmunotherapy and conditioning regimens on clinical outcomes. We identified 228 patients meeting inclusion criteria. Baseline characteristics were similar among the induction groups except for some variation in age. The type of induction chemoimmunotherapy received did not influence overall response rates (ORRs) (0.43), progression-free survival (PFS) (P > .67), or overall survival (OS) (P > .35) on multivariate analysis (PFS and OS). Delivery of autologous stem cell transplant (ASCT) was associated with favorable PFS and OS (0.01) on univariate analysis only this benefit was not seen on multivariate analysis-PFS (0.36) and OS (0.21). Compared with busulfan and melphalan (BuMel), the use of the carmustine, etoposide, cytarabine, melphalan (BEAM)-conditioning regimen was associated with inferior PFS (HR = 2.0 [95% CI 1.1-3.6], 0.02) but not OS (HR = 1.1 [95% CI 0.5-2.3], 0.81) on univariate analysis only. Within the limits of a retrospective study and modest power for some comparisons, type of induction therapy did not influence ORR, PFS, or OS for transplant-eligible patients with MCL. International efforts are required to perform randomized clinical trials evaluating chemoimmunotherapy induction regimens.

Outcomes of synchronous systemic and central nervous system (CNS) involvement of diffuse large B-cell lymphoma are dictated by the CNS disease: a collaborative study of the Australasian Lymphoma Alliance.

Publisher: Wiley

Date: 24-06-2019

DOI: 10.1111/BJH.16064

Abstract: De novo diffuse large B-cell lymphoma (DLBCL) presenting with synchronous central nervous system (CNS) and systemic disease (synDLBCL) is not well described and is excluded from clinical trials. We performed a retrospective analysis of 80 synDLBCL patients treated across 10 Australian and UK centres. Of these patients, 96% had extranodal systemic disease. CNS-directed treatment with combination intravenous cytarabine and high-dose methotrexate ("CNS-intensive") (n = 38) was associated with favourable survival outcomes compared with "CNS-conservative" strategies such as intravenous high-dose methotrexate monotherapy, intrathecal therapy and/or radiotherapy (2-year progression-free survival [PFS] 50% vs. 31%, P = 0·006 2-year overall survival [OS] 54% vs. 44%, P = 0·037). Outcomes were primarily dictated by the ability to control the CNS disease, with 2-year cumulative CNS relapse incidence of 42% and non-CNS relapse 21%. Two-year OS for CNS-relapse patients was 13% vs. 36% for non-CNS relapses (P = 0·02). Autologous stem cell transplantation as consolidation (n = 14) was not observed to improve survival in those patients who received CNS-intensive induction when matched for induction outcomes (2-year PFS 69% vs. 56%, P = 0·99 2-year OS 66% vs. 56%, P = 0·98). Hyperfractionated or infusional systemic treatment did not improve survival compared to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) (2-year OS 49% for both groups). Our study suggests that adequate control of the CNS disease is paramount and is best achieved by intensive CNS-directed induction.

Diagnosis and management of rare gastrointestinal lymphomas

Publisher: Informa UK Limited

Date: 21-06-2012

DOI: 10.3109/10428194.2012.695780

Abstract: Primary gastrointestinal (GI) lymphoma is rare, however accounts for 30-40% of cases of extranodal lymphoma. Several lymphoma subtypes have a propensity for GI tract involvement. Whilst the literature is dominated by data related to the more common extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) and diffuse large B-cell lymphoma (DLBCL) of the stomach, this review focuses on the rare subtypes of enteropathy-associated T-cell lymphoma (EATL), GI follicular lymphoma, mantle cell lymphoma (lymphomatous polyposis coli) and extranodal natural killer (NK)/T-cell lymphoma nasal-type (ENKTL). Due to its rarity, the majority of data regarding primary GI lymphoma have been derived from subgroups of larger cohorts. Clinical characteristics, prognosis and management can differ from those of nodal disease, despite corresponding histology. We discuss these differences and the challenges associated with diagnosis and management of these rare diseases.

Death from mantle cell lymphoma limits sequential therapy, particularly after first relapse: Patterns of care and outcomes in a series from Australia and the United Kingdom

Publisher: Wiley

Date: 30-10-2023

DOI: 10.1111/BJH.19179

Peri-operative chemotherapy in the management of resectable colorectal cancer pulmonary metastases

Publisher: Springer Science and Business Media LLC

Date: 08-2012

DOI: 10.1186/1471-2407-12-326

Abstract: Surgery is often advocated in patients with resectable pulmonary metastases from colorectal cancer (CRC). Our study aims to evaluate peri-operative chemotherapy in patients with metastastic CRC undergoing pulmonary metastasectomy. Patients treated for CRC who underwent pulmonary metastasectomy by a single surgeon were identified. Outcome measures included survival, peri-operative complications, radiological and histological evidence of chemotherapy-induced lung toxicities. Between 1997 and 2009, 51 eligible patients were identified undergoing a total of 72 pulmonary resections. Thirty-eight patients received peri-operative chemotherapy, of whom 9 received an additional biological agent. Five-year overall survival rate was 72% in the whole cohort - 74% and 68% in those who received peri-operative chemotherapy (CS) and those who underwent surgery alone (S) respectively. Five-year relapse free survival rate was 31% in the whole cohort - 38% and ≤18% in CS and S groups respectively. Only 8% had disease progression during neoadjuvant chemotherapy. There were no post-operative deaths. Surgical complications occurred in only 4% of patients who received pre-operative chemotherapy. There was neither radiological nor histological evidence of lung toxicity in resected surgical specimens. Peri-operative chemotherapy can be safely delivered to CRC patients undergoing pulmonary metastasectomy. Survival in this selected group of patients was favourable.

The impact of a multidisciplinary care package for vaccination in needle phobic children: An observational study

Publisher: Wiley

Date: 26-02-2022

DOI: 10.1111/JPC.15928

Abstract: Children with severe needle phobia find vaccination extremely distressing and can remain unvaccinated, which puts them at an increased risk of contracting and transmitting vaccine preventable disease. Referral to a specialist or hospital service may occur when they cannot be safely vaccinated in the community, but engagement of allied health services can be inconsistent. The aim of the study was to assess the impact of a multidisciplinary, consumer‐oriented model of care on vaccinations for needle phobic children. Needle phobic children aged between 6 and 16 years attended multidisciplinary consultation, as part of a care package, to assess previous experiences and determine the level of intervention that was required to support vaccination. A multidisciplinary case meeting followed this appointment and an in idualised plan formulated for each patient. The main outcome of the project was rate of successful vaccination. The care package resulted in a successful vaccination rate of 83% ( n = 20) with 69 vaccines administered across three clinics. Of those successful, 90% required multiple injections per visit. The majority of patients indicated moderate to high level of anxiety. Supportive care was escalated and de‐escalated as tolerated. Results demonstrate the ersity of patients presenting with needle phobia and indicate an in idualised, collaborative approach is preferable to a ‘one size fits all’ model of care. The study highlights a need for the development of guidelines that streamline the assessment and in idualisation of procedural anxiety plans to meet patient needs and embed these processes into standard care.

Immune priming with avelumab and rituximab prior to R-CHOP in diffuse large B-cell lymphoma: the phase II AvR-CHOP study

Publisher: Springer Science and Business Media LLC

Date: 11-03-2023

DOI: 10.1038/S41375-023-01863-7

Optimisation of complex health interventions prior to a randomised controlled trial: a scoping review of strategies used

Publisher: Springer Science and Business Media LLC

Date: 15-03-2016

DOI: 10.1186/S40814-016-0058-Y

Effect of Reasons for Screen Failure on Subsequent Treatment Outcomes in Cancer Patients Assessed for Clinical Trials

Publisher: S. Karger AG

Date: 2019

DOI: 10.1159/000501211

Abstract: b i Introduction: /i /b The cancer research community increasingly question the rigidity of eligibility criteria in clinical trials. Common reasons for “screen failure” (RFSF) are well documented however, their effect on subsequent standard therapy (SST) and outcomes is unclear. b i Methods: /i /b This retrospective study evaluated patients aged ≥18 years with solid malignancy who were listed as ineligible on a screening log between February 2011 and March 2018. Patients screen-failed for biomarker results or incorrect cancer stage rior treatment profile were excluded. Data were collected from electronic hospital records, including demographics, cancer history, RFSF, subsequent therapy, and outcomes. b i Results: /i /b Overall, 217 patients were eligible. The most common histologies were lung (28%), melanoma, colon, and pancreatic (all 11%) 90% were metastatic. The most common RFSF were rapid disease progression (PD 16%), performance status (PS) ≥2 (12%), and abnormal liver function tests (aLFT 12%). After screen failure, 129/217 (59%) had SST 9 were dose-reduced. Treatment-naïve or phase III trial-ineligible patients were more likely to receive SST than those pre-treated or phase I trial-ineligible (72/104 vs. 52/113, i /i = 0.0006 71/109 vs. 15/42, i /i = 0.00013), respectively. RFSF stabilised/improved in 104/217 (48%) the main RFSF was co-morbidity (19/104). The most common RFSF to deteriorate were rapid PD (27/72), PS ≥2 (20/72), and aLFT with liver metastases (LM 13/72). b i Conclusions: /i /b RFSF related to organ function rarely deteriorate unless directly involved with underlying malignancy. Most RFSF do not prevent patients from having SST, nor increase dose reductions, especially in treatment-naïve hase III trial-ineligible patients. Those with RFSF of poor PS, rapid PD, and aLFT from LM are less suitable for SST. Careful broadening of trial eligibility is warranted.

EBV+ CNS LYMPHOMAS HAVE A DISTINCTIVE TUMOR MICROENVIRONMENT AND GENETIC PROFILE, WHICH IS AMENABLE TO COMBINATION 3RD PARTY EBV-SPECIFIC CTL AND IBRUTINIB THERAPY

Publisher: Wiley

Date: 06-2019

DOI: 10.1002/HON.91_2629

Docetaxel and irinotecan as second-line therapy for advanced oesophagogastric cancer

Publisher: Elsevier BV

Date: 05-2011

DOI: 10.1016/J.EJCA.2010.12.021

Abstract: Systemic chemotherapy improves survival in oesophagogastric cancer however no standard second-line regimen exists due to a paucity of randomised data. Docetaxel combined with irinotecan (DI) provides a suitable option due to the lack of cross-reactivity with first-line therapeutics and a tolerable toxicity profile. We retrospectively reviewed a cohort of patients with advanced oesophagogastric cancer in two institutions treated with the combination of docetaxel 35 mg/m(2) plus irinotecan 60 mg/m(2) day 1 and day 8 every 21 days, following progression with first-line platinum-based therapy. Between January 2000 and September 2009, 41 eligible patients were identified. Median age was 58 years, male:female 25:16, adenocarcinoma:squamous cell carcinoma 37:4, oesophageal:oesophagogastric junction:gastric 7:10:24. Locally advanced:metastatic disease 6:35. Previous radical surgery:radiotherapy:both 6:4:7. 27/41 had progressed within 90 days of receiving platinum-based therapy. Median number of chemotherapy cycles: 3 (range 1-12). Eight patients required dose reductions due to DI toxicity. 10/28 evaluable patients had a response, median progression-free survival (PFS) was 11 weeks (95% confidence intervals (CI): 9-13 weeks) with median overall survival 24 weeks (95%CI: 12-35 weeks). No significant prognostic factors were identified. Weekly docetaxel combined with irinotecan has acceptable safety and modest efficacy in the second-line treatment of advanced oesophagogastric cancer. Further prospective evaluation of this regimen is warranted.

Outcomes following front-line chemotherapy in peripheral T-cell lymphoma: 10-year experience at The Royal Marsden and The Christie Hospital

Publisher: Informa UK Limited

Date: 09-11-2017

DOI: 10.1080/10428194.2017.1393671

Abstract: We evaluated the outcomes for patients with peripheral T-cell lymphoma (PTCL) undergoing front-line chemotherapy at our institutions between 2002 and 2012. One hundred and fifty-six patients were eligible, comprising PTCL not otherwise specified (NOS) (n = 50, 32.0%), angioimmunoblastic T-cell lymphoma (AITL) (n = 44, 28.2%), anaplastic large-cell lymphoma (ALCL) ALK negative (n = 23, 14.7%), ALCL ALK positive (n = 16, 10.3%), and other (n = 23, 14.7%). Most patients received CHOP (66.0%) and 13.0% received an autologous hematopoietic progenitor cell transplant (HPCT). With a median follow-up of 63.4 months, 5-year overall survival (OS) and progression-free survival (PFS) was 38.8% and 19.8% respectively. Independent risk factors for inferior OS were age >60 years, International Prognostic Index (IPI) ≥ 2 and lack of complete response to induction. When responding patients were compared by receipt of an autologous HPCT versus not, HPCT was associated with improved PFS (p = .001) and OS (p = .046) and remained significant for PFS in multivariate analysis suggesting a possible therapeutic benefit.

A dose escalation study of gemcitabine plus oxaliplatin in combination with imatinib for gemcitabine-refractory advanced pancreatic adenocarcinoma

Publisher: Elsevier BV

Date: 04-2012

DOI: 10.1093/ANNONC/MDR317

Abstract: Targeting platelet-derived growth factor receptor-β (PDGFR-β) is a potential strategy to reduce tumour-related interstitial fluid pressure, enhance cytotoxic drug uptake and reduce chemoresistance. This study aimed to define safe doses of gemcitabine plus oxaliplatin when combined with imatinib (potent PDGFR-β inhibitor) in patients with advanced gemcitabine-refractory pancreatic cancer (PC). Using a 3 + 3 dose escalation design, patients of performance status zero or one were entered into five sequential dose levels (DLs) of gemcitabine [day 1, from 400 (DL1) to 1000 mg/m(2) (DL4)] and oxaliplatin [day 2, 85 (DL1-4) and 100 mg/m(2) (DL5)] two weekly. Imatinib 400 mg od was given for 7 days (day minus 2-5) each cycle. Twenty-seven patients received 168 cycles in total. Median age was 61 years (44-74 years). Dose-limiting toxicities occurred in two of two patients at DL5 (G4 thrombocytopenia, G3 lethargy), defined as the maximum tolerated dose and one of six patients at DL4 (G3 lethargy). DL4 was expanded. There were 2 of 27 partial responses and 14 of 27 stable disease [disease control 52%, 95% confidence interval (CI) 32% to 71%]. Median progression-free survival and overall survival were 4.6 (95% CI 2.1-7.0) and 5.6 months (95% CI 2.5-8.7), respectively. In gemcitabine-refractory PC, gemcitabine (1000 mg/m(2)) and oxaliplatin (85 mg/m(2)) can be safely combined with imatinib given on a 7 days on and 7 days off intermittent schedule.

Molecular associations of response to the new-generation BTK inhibitor zanubrutinib in marginal zone lymphoma

Publisher: American Society of Hematology

Date: 14-07-2023

DOI: 10.1182/BLOODADVANCES.2022009412

Abstract: Using tissue whole exome sequencing (WES) and circulating tumor cell–free DNA (ctDNA), this Australasian Leukaemia & Lymphoma Group translational study sought to characterize primary and acquired molecular determinants of response and resistance of marginal zone lymphoma (MZL) to zanubrutinib for patients treated in the MAGNOLIA clinical trial. WES was performed on baseline tumor s les obtained from 18 patients. For 7 patients, ctDNA sequence was interrogated using a bespoke hybrid-capture next-generation sequencing assay for 48 targeted genes. Somatic mutations were correlated with objective response data and survival analysis using Fisher exact test and Kaplan-Meier (log-rank) method, respectively. Baseline WES identified mutations in 33 of 48 (69%) prioritized genes. NF-κB, NOTCH, or B-cell receptor (BCR) pathway genes were implicated in s les from 16 of 18 patients (89%). KMT2D mutations (n = 11) were most common, followed by FAT1 (n = 9), NOTCH1, NOTCH2, TNFAIP3 (n = 5), and MYD88 (n = 4) mutations. MYD88 or TNFAIP3 mutations correlated with improved progression-free survival (PFS). KMT2D mutations trended to worse PFS. Acquired resistance mutations PLCG2 (R665W/R742P) and BTK (C481Y/C481F) were detected in 2 patients whose disease progressed. A BTK E41K noncatalytic activating mutation was identified before treatment in 1 patient who was zanubrutinib-refractory. MYD88, TNFAIP3, and KMT2D mutations correlate with PFS in patients with relapsed/refractory MZL treated with zanubrutinib. Detection of acquired BTK and PLCG2 mutations in ctDNA while on therapy is feasible and may herald clinical disease progression. This trial was registered at anzctr.org.au/ as #ACTRN12619000024145.

Predicting primary treatment failure using interim FDG‐PET scanning in diffuse large B‐cell lymphoma

Publisher: Wiley

Date: 22-07-2021

DOI: 10.1111/EJH.13684

Abstract: Interim FDG‐PET (iPET) in diffuse large B‐cell lymphoma (DLBCL) is increasingly practised and used in clinical trials to adapt further therapy. However, the optimum timing and methodology of iPET remains controversial. We retrospectively analysed the iPET results and outcomes of 200 DLBCL patients where FDG‐PET was routinely performed at baseline, after 2 cycles (iPET2) and at completion of chemoimmunotherapy. iPET was also performed after 4 cycles (iPET4) where at iPET2, Deauville score (DS) was ≥4. Scans were assessed by blinded expert lymphoma PET physicians for DS, maximum standard uptake value (SUVmax), total metabolic tumour volume (TMTV) and total lesion glycolysis (TLG). Treatment failure was defined as death, progression or refractory disease. 95.5% of patients received R‐CHOP. No baseline PET parameter was predicted for EFS or OS independent of the NCCN‐IPI. The multivariable analysis at iPET2 showed DS5 (19.5% of cases) predicted treatment failure (HR 6.29, 95% CI 3.01‐13.17, P .001), but DS4 was equivalent to DS1‐3. At iPET4, ΔSUVmax 66% predicted treatment failure (HR 5.49, 95% CI 3.03‐9.99, P .001). By multivariable analysis of all time points, high NCCN‐IPI and DS5 at iPET2 were negative predictors of survival. These findings were independent of novel prognostic markers.

Hodgkin lymphoma: an Australian experience of ABVD chemotherapy in the modern era

Publisher: Springer Science and Business Media LLC

Date: 15-02-2016

DOI: 10.1007/S00277-016-2611-4

Abstract: Approximately 560 new cases of Hodgkin lymphoma (HL) are diagnosed annually in Australia. Standard first-line therapy is ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine). It is unknown how survival outcomes in patients receiving ABVD in current clinical practice, with routine positron emission tomography (PET) imaging and modern supportive measures, compare with results from published trials. This is a retrospective multi-centre study of patients with previously untreated HL between November 1999 and December 2014 receiving ABVD induction. Baseline characteristics, treatment details, toxicity and outcome data were collected from hospital records. The primary endpoint was overall survival (OS). Secondary endpoints included overall response rate (ORR), progression-free survival (PFS), response to treatment and toxicity. One hundred and eighty-nine eligible patients were identified. Median age was 32 years (range 17-79). Nodular-sclerosing HL was the most common subtype (78 %), 44 % had B symptoms and 11 % had marrow involvement. Median number of cycles of ABVD administered was 6 (range 3-8). Eighteen patients (11 %) had dose delay, 21 (13 %) had dose reductions and 11 (8 %) had both. The ORR, defined predominantly by PET scan, was 96 % (CR 89 %). Five-year OS and PFS were 93 and 84 %, respectively in early disease (stage I-IIA) and 89 and 63 % in advanced disease (stage IIB, III and IV). No poor prognostic factors were identified on multivariate testing. The most common grade 3/4 toxicity was neutropenia (53 %). Our study confirms the excellent prognosis and manageable toxicity in HL patients receiving ABVD in phase III studies are reflected in patients treated in routine clinical practice in the modern era.

Treatment of metastatic colorectal cancer: focus on panitumumab.

Publisher: Informa UK Limited

Date: 06-2015

DOI: 10.2147/CMAR.S71821

Echocardiography has low utility in cancer patients with Staphylococcus aureus bacteraemia: findings from a retrospective study

Publisher: Springer Science and Business Media LLC

Date: 21-03-2018

DOI: 10.1007/S00520-018-4162-9

Abstract: To describe the incidence of infective endocarditis (IE) detected on echocardiography in cancer patients with confirmed Staphylococcus aureus bacteraemia (SAB). We retrospectively identified 95 cases of SAB in cancer patients from January 2007-March 2016. Echocardiography was ordered at the discretion of the treating team, and positive findings defined according to the Modified Duke Criteria. Complicated bacteraemia was defined by prolonged bacteraemia, presence of intracardiac device rosthetic valve, or signs of metastatic infection. Major predisposing risk factors for IE (intracardiac device, prosthetic valve, valvular disease, diabetes mellitus, renal dialysis) were present in 27% of cases. Fifty-one of 95 (54%) had a central venous catheter and 17 (18%) patients had complicated bacteraemia. Echocardiography was performed in 75/95 (79%) episodes, with transthoracic echocardiography (TTE) alone in 56, transoesophageal echocardiography (TOE) alone in 4 and both in 15. Echocardiography was diagnostic for IE in 2 patients (1 TTE, 1 TOE), including one result that led to the diagnosis of IE in a clinically unsuspected case. Four further cases of IE were diagnosed on clinical findings, resulting in an overall rate of IE of 6% (6/95). Five of these cases occurred in patients with complicated bacteraemia or ≥ 1 risk factor for IE. No patient was readmitted due to IE. IE is infrequent in cancer patients with uncomplicated SAB and no risk factors for IE. Performing echocardiography routinely in all cancer patients with SAB rarely alters diagnosis or affects antibiotic management and therefore should be reserved for patients with specific risk factors.

Cancer-related cognitive impairment in patients with newly diagnosed aggressive lymphoma undergoing standard chemotherapy: a longitudinal feasibility study

Publisher: Springer Science and Business Media LLC

Date: 14-06-2022

DOI: 10.1007/S00520-022-07153-9

Abstract: Cancer-related cognitive impairment (CRCI) is a recognised adverse consequence of cancer and its treatment. This study assessed the feasibility of collecting longitudinal data on cognition in patients with newly diagnosed, aggressive lymphoma undergoing standard therapy with curative intent via self-report, neuropsychological assessment, peripheral markers of inflammation, and neuroimaging. An exploration and description of patterns of cancer-related cognitive impairment over the course of treatment and recovery was also undertaken and will be reported separately. Eligible participants completed repeated measures of cognition including self-report and neuropsychological assessment, and correlates of cognition including blood cell–based inflammatory markers, and neuroimaging at three pre-specified timepoints, time 1 (T1) — pre-treatment (treatment naïve), time 2 (T2) — mid-treatment, and time 3 (T3) — 6 to 8 weeks post-completion of treatment. 30/33 eligible patients (91%, 95% CI: 76%, 97%) were recruited over 10 months. The recruitment rate was 3 patients/month (95% CI: 2.0, 4.3 patients/month). Reasons for declining included feeling overwhelmed and rapid treatment commencement. Mean age was 57 years (SD = 17 years) and 16/30 (53%) were male. Most patients (20/30, 67%) had diffuse large B cell lymphoma or Hodgkin lymphoma (4/30, 13%). The neuroimaging sub-study was optional, 11/30 participants (37%) were eligible to take part, and all agreed. The remaining 19 participants were ineligible as their diagnostic PET/CT scan was completed prior. Retention and compliance with all assessments were 89 to 100% at all timepoints. Only one participant was withdrawn due to disease progression. Findings from this study including excellent recruitment, retention, and compliance rates demonstrate it is feasible to longitudinally assess cognition in people with newly diagnosed aggressive lymphoma during their initial treatment and recovery to inform the development of future research to improve patient experiences and cognitive outcomes. Trial registration. Australian New Zealand Clinical Trials Registry ACTRN12619001649101.

Avelumab in Combination Regimens for Relapsed/Refractory DLBCL: Results from the Phase Ib JAVELIN DLBCL Study

Publisher: Springer Science and Business Media LLC

Date: 23-10-2021

DOI: 10.1007/S11523-021-00849-8

Dalotuzumab in chemorefractory KRAS exon 2 mutant colorectal cancer: Results from a randomised phase II/III trial

Publisher: Wiley

Date: 17-10-2016

DOI: 10.1002/IJC.30453

Abstract: Limited data are available on the efficacy of anti-IGF-1R agents in KRAS mutant colorectal cancer (CRC). We analysed the outcome of 69 chemorefractory, KRAS exon 2 mutant CRC patients who were enrolled in a double-blind, randomised, phase II/III study of irinotecan and cetuximab plus dalotuzumab 10 mg/kg once weekly (arm A), dalotuzumab 7.5 mg/kg every second week (arm B) or placebo (arm C). Objective response rate (5.6% vs. 3.1% vs. 4.8%), median progression-free survival (2.7 vs. 2.6 vs. 1.4 months) and overall survival (7.8 vs. 10.3 vs. 7.8 months) were not statistically significantly different between treatment groups. Most common grade ≥3 treatment-related toxicities included neutropenia, diarrhoea, hyperglycaemia, fatigue and dermatitis acneiform. Expression of IGF-1R, IGF-1, IGF-2 and EREG by quantitative real-time polymerase chain reaction was assessed in 351 patients from the same study with available data on KRAS exon 2 mutational status. Median cycle threshold values for all biomarkers were significantly lower (i.e., higher expression, p < 0.05) among patients with KRAS wild-type compared to those with KRAS exon 2 mutant tumours. No significant changes were found according to location of the primary tumour with only a trend towards lower expression of IGF-1 in colon compared to rectal cancers (p = 0.06). Albeit limited by the small s le size, this study does not appear to support a potential role for anti-IGF-1R agents in KRAS exon 2 mutant CRC. Data on IGF-1R, IGF-1 and IGF-2 expression here reported may be useful for patient stratification in future trials with inhibitors of the IGF pathway.

Are We Ready To Stratify Treatment for Diffuse Large B-Cell Lymphoma Using Molecular Hallmarks?

Publisher: Oxford University Press (OUP)

Date: 18-10-2012

DOI: 10.1634/THEONCOLOGIST.2012-0218

Abstract: After completing this course, the reader will be able to: Describe the oncogenic drivers in DLBCL, especially those that have recently been identified, and how they relate to the oncogenic DLBCL subtypes.Describe the prognostic and potentially predictive implications of DLBCL COO subtype for chemotherapy and rituximab.Outline the evidence for novel targeted therapies and therapeutic strategies in DLBCL, how they may be stratified by DLBCL subtype or to specific tumor molecular features, and how these strategies can be incorporated into current treatment paradigms and prospective clinical trial design. CME This article is available for continuing medical education credit at CME.TheOncologist.com The ision of the heterogeneous entity of diffuse large B-cell lymphoma (DLBCL) into the ontogenic phenotypes of germinal center B-cell-like (GCB) and activated B-cell-like (ABC) is optimally determined by gene expression profiling (GEP), although simpler immunohistochemistry (IHC) algorithms are alternatively being used. The cell-of-origin (COO) classification assists in prognostication and may be predictive of response to therapy. Mounting data suggests that IHC methods of classifying COO may be inaccurate. GEP categorization of COO is superior in defining prognostically and biologically distinct DLBCL subtypes, but current barriers to its widescale use include inaccessibility, cost, and lack of methodological standardization and prospective validation. The poorer prognosis of ABC-DLBCL is frequently associated with constitutive activity in the NF-κB pathway and aberrations in upstream or downstream regulators of this pathway. The molecular mechanisms underlying lymphomagenesis in GCB-DLBCL are arguably less well defined, but C-REL lification and mutations in BCL-2 and EZH2 are common. New technologies, such as next-generation sequencing, are rapidly revealing novel pathogenic genetic aberrations, and DLBCL treatment strategies are increasingly being designed focusing on distinctive pathogenic drivers within ontogenic phenotypes. This review examines emerging molecular targets and novel therapeutic agents in DLBCL, and discusses whether stratifying therapy for DLBCL using molecular features is merited by current preclinical and clinical evidence.

Relationship Between Colorectal Cancer Biomarkers and Response to Epidermal Growth Factor Receptor Monoclonal Antibodies

Publisher: American Society of Clinical Oncology (ASCO)

Date: 10-2010

DOI: 10.1200/JCO.2010.29.5626

Routine blood investigations have limited utility in surveillance of aggressive lymphoma in asymptomatic patients in complete remission

Publisher: Springer Science and Business Media LLC

Date: 23-07-2018

DOI: 10.1038/S41416-018-0183-X

Systemic ALCL Treated in Routine Clinical Practice: Outcomes Following First-Line Chemotherapy from a Multicentre Cohort

Publisher: Springer Science and Business Media LLC

Date: 26-05-2021

DOI: 10.1007/S12325-021-01764-0

Quantifying exposure to diagnostic medical radiation in patients with inflammatory bowel disease: are we contributing to malignancy?

Publisher: Wiley

Date: 21-07-2007

DOI: 10.1111/J.1365-2036.2007.03449.X

Abstract: While potential risks of diagnostic medical radiation are acknowledged, actual exposure of patients in routine clinical practice is poorly documented. To quantify such exposure to vulnerable abdominal organs in patients with inflammatory bowel disease who are already at risk of intestinal cancer. All incidences of exposure to diagnostic medical radiation were documented in a consecutive series of 100 patients with inflammatory bowel disease (62 Crohn's disease, 37 ulcerative colitis, 1 indeterminate colitis) attending a hospital-based clinic. Total effective dose (mSv) was calculated using published tables. Predictors of high or no irradiation were evaluated by multivariate logistic regression analysis. Thirteen patients had no documented diagnostic irradiation. Twenty-three patients received an effective dose greater than 25 mSv. An at-risk effective dose >50 mSv was received by 11 patients. Dosage was higher in patients with Crohn's disease than ulcerative colitis (P = 0.02) and in patients undergoing surgery (P = 0.004). However, no predictive factors for high radiation dosage or for no exposure were identified. At-risk irradiation from diagnostic medical radiation is common in patients with inflammatory bowel disease, and might potentially contribute to the elevated risk of intra-abdominal and other cancers. The level of irradiation should be considered in clinical decisions regarding abdominal imaging.

Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R‐CHOP) in the management of primary mediastinal B‐cell lymphoma: a subgroup analysis of the UK NCRI R‐

Publisher: Wiley

Date: 08-2016

DOI: 10.1111/BJH.14287

Abstract: We performed a subgroup analysis of the phase III UK National Cancer Research Institute R-CHOP-14 versus R-CHOP-21 (two- versus three-weekly rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone) trial to evaluate the outcomes for 50 patients with World Health Organization 2008 classified primary mediastinal B-cell lymphoma identified from the trial database. At a median follow-up of 7·2 years the 5-year progression-free survival and overall survival was 79·8% and 83·8%, respectively. An exploratory analysis raised the possibility of a better outcome in those who received R-CHOP-14 and time intensification may still, in the rituximab era, merit testing in a randomised trial in this subgroup of patients.

Upper Gastrointestinal Malignancies: A New Era in Clinical Colorectal Cancer

Publisher: Elsevier BV

Date: 10-2009

DOI: 10.3816/CCC.2009.N.030

Characteristics and Outcomes of Older Patients With Classical Hodgkin Lymphoma: An Australasian Lymphoma Alliance, and Lymphoma and Related Diseases Registry Study

Publisher: Elsevier BV

Date: 05-2023

DOI: 10.1016/J.CLML.2023.01.014

Mycosis fungoides and Sézary syndrome: Australian clinical practice statement

Publisher: Wiley

Date: 26-12-2020

DOI: 10.1111/AJD.13467

Abstract: Primary cutaneous lymphomas represent a heterogeneous group of T‐ and B‐cell lymphomas with distinct clinical presentations, histopathologic features, treatment approaches and outcomes. The cutaneous T‐cell lymphomas, which include mycosis fungoides and Sézary syndrome, account for the majority of the cutaneous lymphomas. This Clinical Practice Statement is reflective of the current clinical practice in Australia. An expanded form of the Clinical Practice Statement (and updates), along with helpful patient resources and access to support groups, can be found at the following ( www.australasianlymphomaalliance.org.au ).

Evolution of eligibility criteria for diffuse large B‐cell lymphoma randomised controlled trials over 30 years

Publisher: Wiley

Date: 14-04-2021

DOI: 10.1111/BJH.17436

Abstract: Eligibility criteria for randomised control trials (RCT) in diffuse large B‐cell lymphoma (DLBCL) may be becoming increasingly strict. In this analysis, 42 first‐line phase III RCTs enrolling DLBCL patients since 1990 were identified from PubMed and clinicaltrials.gov . Changes in 31 in idual eligibility criteria were assessed using three pre‐defined eras [(1) 1993–2005 (2) 2006–2013 and (3) 2014–2020]. The presence of 15/31 criteria increased significantly over time, and the total number of criteria per study also increased over time [median Era 1: 14·5, interquartile range (IQR) 12·6–16·4 Era 2: 21, 18·8–23·3 Era 3: 23, 21–25 P 0·001]. When each trial's eligibility criteria were applied to 215 consecutive patients from an institutional database treated between 2010 and 2020, a median of 57% (IQR 47–70) of patients were hypothetically eligible for trial enrolment. The median percentage of patients eligible was 68% (56–91), 54% (37–81) and 47% (38–82) for Era 1, 2 and 3 respectively ( P = 0·004). Phase III front‐line DLBCL trial criteria have become increasingly restrictive over the last three decades, resulting in a diminishing proportion of trial‐eligible patients, with less than 50% of our patients eligible for modern‐era studies. This potentially impacts generalisability of recent trial results and will likely limit recruitment to ongoing studies.

Can PET eradicate irradiation in PMBCL?

Publisher: American Society of Hematology

Date: 10-12-2020

DOI: 10.1182/BLOOD.2020007766

Toxicity associated with high-dose intravenous methotrexate for hematological malignancies.

Publisher: Informa UK Limited

Date: 16-05-2022

DOI: 10.1080/10428194.2022.2074987

Abstract: Intravenous high-dose methotrexate (HD-MTX) is a critical chemotherapeutic agent in hematological malignancies, however, data are lacking on how to predict and prevent toxicities such as kidney injury. We retrospectively analyzed 539 episodes of HD-MTX (≥1 g/m 2 ) delivered to 144 patients for treatment of prophylaxis of CNS hematological malignancy across three Australian institutions and correlated risk factors with toxicity. Clinically relevant (CTCAE v4.03 grade 2-4) nephrotoxicity occurred on 36 (7%) occasions and was mostly grade 2. Multivariate analysis revealed that doses ≥6 g/m 2 (HR 5.02, 95%CI 1.46-17.2, p = 0.01) and interacting/nephrotoxic drugs (HR: 7.15, 91%CI: 2.18-23.512, p = 0.001) were the only factors associated with nephrotoxicity. 48-hour methotrexate level, hypoalbuminemia and increasing age were associated with prolonged clearance but not nephrotoxicity. Mucositis, liver dysfunction and cytopenias were transient and mild in most cases. We have demonstrated that the most common risk factors for nephrotoxicity are modifiable which may assist clinical decision-making when administering this important drug.

Cytarabine-based induction immunochemotherapy in the front-line treatment of older patients with mantle cell lymphoma

Publisher: Springer Science and Business Media LLC

Date: 19-09-2019

DOI: 10.1038/S41598-019-49776-9

Abstract: The role of cytarabine-based induction and autologous stem cell transplantation (ASCT) in front-line treatment of younger patients with mantle cell lymphoma (MCL) is well established, however the utility of intensive approaches in older patients remains unclear. This retrospective study compared first line treatment outcomes in patients aged 60 years or more, treated at six tertiary centres between 2000–2015. 70 patients included had a median age of 69 (60–91) and most (94%) demonstrated advanced stage disease. Treatment regimens included: R-CHOP-like (n = 39), alternating R-CHOP/R-DHAC (n = 10), R-HyperCVAD/R-MA (n = 7), R-CHOP/Cytarabine (Nordic Protocol) (n = 10) and other (n = 4). 16 patients underwent an ASCT. The median follow-up for surviving patients was 37 months. Compared to R-CHOP-like therapies, cytarabine-based regimens were associated with an improved overall response rate (ORR) of 70% vs 33% (p 0.001) and overall survival (OS) (HR 0.541, [0.292–1.001], p = 0.05). No difference in efficacy between different cytarabine-based regimens was detected, but R-HyperCVAD/R-MA was associated with increased hospitalisation and transfusion requirements. Patients undergoing ASCT demonstrated an improved median OS (HR 0.108 [0.015–0.796], p = 0.029) but were significantly younger. These results reaffirm the use of cytarabine in MCL for selected patients aged over 60. Such regimens should be strongly considered for this population in frontline therapy.

Novel Indications for Bruton's Tyrosine Kinase Inhibitors, beyond Hematological Malignancies.

Publisher: MDPI AG

Date: 21-03-2018

DOI: 10.3390/JCM7040062

Abstract: Bruton’s tyrosine kinase (BTK) is a critical terminal enzyme in the B-cell antigen receptor (BCR) pathway. BTK activation has been implicated in the pathogenesis of certain B-cell malignancies. Targeting this pathway has emerged as a novel target in B-cell malignancies, of which ibrutinib is the first-in-class agent. A few other BTK inhibitors (BTKi) are also under development (e.g., acalabrutinib). While the predominant action of BTKi is the blockade of B-cell receptor pathway within malignant B-cells, increasing the knowledge of off-target effects as well as a potential role for B-cells in proliferation of solid malignancies is expanding the indication of BTKi into non-hematological malignancies. In addition to the expansion of the role of BTKi monotherapy, combination therapy strategies utilizing ibrutinib with established regimens and combination with modern immunotherapy compounds are being explored.

GEM-P chemotherapy is active in the treatment of relapsed Hodgkin lymphoma

Publisher: Springer Science and Business Media LLC

Date: 26-10-2013

DOI: 10.1007/S00277-013-1930-Y

Abstract: Hodgkin lymphoma (HL) is a relatively chemosensitive malignancy. However, for those who relapse, high-dose chemotherapy with autologous stem cell transplant is the treatment of choice which relies on adequate disease control with salvage chemotherapy. Regimens commonly used often require inpatient administration and can be difficult to deliver due to toxicity. Gemcitabine and cisplatin have activity in HL, non-overlapping toxicity with first-line chemotherapeutics, and may be delivered in an outpatient setting. In this retrospective single-centre analysis, patients with relapsed or refractory HL treated with gemcitabine 1,000 mg/m(2) day (D)1, D8 and D15 methylprednisolone 1,000 mg D1-5 and cisplatin 100 mg/m(2) D15, every 28 days (GEM-P) were included. Demographic, survival, response and toxicity data were recorded. Forty-one eligible patients were identified: median age 27. One hundred and twenty-two cycles of GEM-P were administered in total (median 3 cycles range 1-6). Twenty of 41 (48 %) patients received GEM-P as second-line treatment and 11/41 (27 %) as third-line therapy. Overall response rate (ORR) to GEM-P in the entire cohort was 80 % (complete response (CR) 37 %, partial response 44 %) with 14/15 CR confirmed as a metabolic CR on PET and ORR of 85 % in the 20 second-line patients. The most common grade 3/4 toxicities were haematological: neutropenia 54 % and thrombocytopenia 51 %. Median follow-up from the start of GEM-P was 4.5 years. Following GEM-P, 5-year progression-free survival was 46 % (95 % confidence interval (CI), 30-62 %) and 5-year overall survival was 59 % (95 % CI, 43-74 %). Fourteen of 41 patients proceeded directly to autologous transplant. GEM-P is a salvage chemotherapy with relatively high response rates, leading to successful transplantation in appropriate patients, in the treatment of relapsed or refractory HL.

Management and Outcomes of Diffuse Large B-cell Lymphoma Post-transplant Lymphoproliferative Disorder in the Era of PET and Rituximab: A Multicenter Study From the Australasian Lymphoma Alliance.

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 11-10-2021

DOI: 10.1097/HS9.0000000000000648

Molecular profiling of colorectal pulmonary metastases and primary tumours: implications for targeted treatment

Publisher: Impact Journals, LLC

Date: 11-04-2017

DOI: 10.18632/ONCOTARGET.17048

Diffuse large B‐cell lymphoma

Publisher: Wiley

Date: 12-07-2023

DOI: 10.1002/HON.3202

Abstract: Large B‐cell lymphoma, the prototype of aggressive non‐Hodgkin lymphomas, is both the most common lymphoma and accounts for the highest global burden of lymphoma‐related deaths. For nearly 4 decades, the goal of treatment has been “cure”, first based on CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), and subsequently with rituximab plus CHOP. However, there is significant clinical, pathologic, and biologic heterogeneity, and not all patients are cured. Understanding and incorporating this biologic heterogeneity into treatment decisions unfortunately is not yet standard of care. Despite this gap, we now have significant advances in frontline, relapsed, and refractory settings. The POLARIX trial shows, for the first time, improved progression‐free survival in a prospective randomized phase 3 setting. In the relapsed and refractory settings, there are now many approved agents/regimens, and several bispecific antibodies poised to join the arsenal of options. While chimeric antigen receptor T‐cell therapy is discussed in detail elsewhere, it has quickly become an excellent option in the second‐line setting and beyond. Unfortunately, special populations such as older adults continue to have poor outcomes and be underrepresented in trials, although a new generation of trials aim to address this disparity. This brief review will highlight the key issues and advances that offer improved outcomes to an increasing portion of patients.

Clinical characteristics of Australian treatment‐naïve patients with classical Hodgkin lymphoma from the lymphoma and related diseases registry

Publisher: Wiley

Date: 28-12-2022

DOI: 10.1111/EJH.13915

Abstract: Comprehensive clinical characteristics of Australian patients with classical Hodgkin Lymphoma (cHL) have not previously been systematically collected and described. We report real‐world data of 498 eligible patients from the first 5 years of the Lymphoma and Related Diseases Registry (LaRDR), including baseline characteristics, histologic subtype, and treatment patterns in first‐line therapy. Patient demographics and distribution of histopathological subtypes of cHL are similar to reported international cohorts. Doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) was the most common therapy for both early and advanced‐stage disease, and 48% of patients with the early‐stage disease received radiotherapy. Treatment patterns are consistent with international guidelines. In comorbid patients ≥60 years of age with advanced‐stage disease, there is greater variation in treatment. In patients with a recorded response, the objective response rate (ORR) was 96% in early‐stage disease, and 88% in advanced‐stage disease. Early progression‐free survival data suggest Australian patients with cHL have good outcomes, similar to other international studies.

The diagnostic and therapeutic challenges of Grade 3B follicular lymphoma.

Publisher: Wiley

Date: 11-03-2021

DOI: 10.1111/BJH.17404

Abstract: Grade 3B follicular lymphoma (G3B FL) is rare, accounting for only 5-10% of FLs. Not only has it been routinely excluded from clinical trials, but data published on diagnosis, outcomes, choice of therapies and role of imaging are conflicting. With the advent of increasingly erse treatment options for low-grade (G1-3A) FL, and the molecular subcategorisation of high-grade B-cell lymphomas, characterisation and treatment of G3B FL is ever more important as extrapolation of data becomes more difficult. New data have emerged exploring unique genetic characteristics, specific features on positron emission tomography imaging, choice of therapy, and outcomes of G3B FL in the current era. The present review will summarise and appraise these new data, and offer recommendations based on current evidence.

Rare case of precursor B-cell acute lymphoblastic leukemia presenting as a solitary paraspinal mass alone.

Publisher: American Society of Clinical Oncology (ASCO)

Date: 08-2013

DOI: 10.1200/JCO.2012.47.2308

Outcomes for transformed follicular lymphoma in the rituximab era: the Royal Marsden experience 2003–2013

Publisher: Informa UK Limited

Date: 08-12-2016

DOI: 10.1080/10428194.2016.1265114

Abstract: Survival for transformed follicular lymphoma (tFL) has improved in the rituximab era and the need for upfront stem cell transplantation (SCT) is unclear. We evaluated the outcomes for all patients treated with first-line chemotherapy for histologically-proven tFL at our institution from 2003-2013 (n = 87). The majority of patients (89.7%) did not receive a SCT as part of first-line management. With a median follow-up of 7.8 years the 5-year overall survival (OS) for all patients was 61.7%. Patients treated with R-CHOP without upfront SCT (n = 55/87) had a 5-year OS of 64.3%. In a Cox regression analysis of the entire cohort (n = 87) International Prognostic Index (IPI) risk group and presence of B symptoms at transformation were independently associated with OS in multivariate analysis (MVA). Our analysis confirms the improved survival of tFL in the rituximab era even in the absence of upfront SCT consolidation.

Prognostic indices in diffuse large B‐cell lymphoma in the rituximab era: an analysis of the UK National Cancer Research Institute R‐CHOP 14 versus 21 phase 3 trial

Publisher: Wiley

Date: 20-05-2020

DOI: 10.1111/BJH.16691

Safety and efficacy of atezolizumab with rituximab and CHOP in previously untreated diffuse large B-cell lymphoma.

Publisher: American Society of Hematology

Date: 14-04-2022

DOI: 10.1182/BLOODADVANCES.2022008344

Abstract: Rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) is the current standard therapy for patients with diffuse large B-cell lymphoma (DLBCL) and is curative in ∼60% of patients. Atezolizumab is a humanized immunoglobulin G1 monoclonal antibody that targets programmed death-ligand 1 and has previously shown anti-tumor activity in several tumor types. In a phase 1b/2 trial (NCT02596971) we evaluated the safety and efficacy of atezolizumab in combination with R-CHOP (atezo-R-CHOP for 6 to 8 cycles) in patients with previously untreated DLBCL. Patients achieving a complete response at the end of induction received consolidation therapy with atezolizumab on Day 1 of each 21-day cycle for an additional 17 cycles. Overall, 42 patients with DLBCL were included in this analysis. The primary endpoint, complete response rate at end of induction, as assessed by an independent review committee (IRC modified Lugano 2014) was 77.5% (95% confidence interval [CI], 64.0-87.7 n = 40). Investigator-assessed progression-free survival and overall survival at 3 years were 77.4% (95% CI, 59.7-88.0) and 87.2% (95% CI, 71.9-94.5), respectively. All treated patients experienced ≥1 adverse event (AE 32 patients [76.2%] had a Grade 3-4 AE). One patient had a fatal AE (unconfirmed progressive multifocal leukoencephalopathy), that was considered related to atezolizumab and rituximab, and 17 (40.5%) patients experienced atezolizumab-related AEs of special interest. In previously untreated patients with DLBCL, atezo-R-CHOP demonstrated encouraging clinical efficacy and a safety profile consistent with the known toxicities of the in idual drugs.

Tumour cell surface antigen targeted therapies in B-cell lymphomas: Beyond rituximab

Publisher: Elsevier BV

Date: 2017

DOI: 10.1016/J.BLRE.2016.08.001

Abstract: Recent proliferation of novel targeted therapies in lymphoma has been substantial. B-cell receptor pathway inhibitors and immune checkpoint inhibitors have been a major focus, however significant advances in monoclonal antibodies (MoAbs) which directly target malignant cells have also occurred. These MoAbs continue to make significant impact in lymphoma management. Novel dosing schedules of anti-CD20 MoAb rituximab potentially optimise efficacy in specific lymphoma subgroups, as certain populations may be receiving suboptimal doses using current schedules. Next-generation anti-CD20 MoAbs may surpass rituximab in terms of efficacy. MoAbs targeting other B-cell surface antigens and antibody-drug conjugates (ADCs) have yielded promising data. Bispecific antibodies that can recruit T-lymphocytes to lymphoma cells have also shown efficacy. To further improve outcomes for patients with lymphoma using MoAbs, scrupulous trial design incorporating translational research, and synergistic drug combinations will be required. This review discusses the mechanisms of action, current data and future directions involving MoAbs.

Integration of Biologic Agents With Cytotoxic Chemotherapy in Metastatic Colorectal Cancer

Publisher: Elsevier BV

Date: 12-2011

DOI: 10.1016/J.CLCC.2011.04.001

Abstract: Colorectal cancer (CRC) remains a leading cause of cancer death in the developed world. Metastatic disease eventually develops in nearly 50% of patients with CRC. Chemotherapy is the mainstay of treatment in metastatic CRC (mCRC) however the majority of patients remain incurable with current therapeutic options. Progress made in the field of surgery, locoregional treatment for low-volume metastatic disease, and systemic chemotherapy has created new treatment paradigms and improved survival in mCRC. Development of new cytotoxic drugs and the advent of targeted agents over the past decade have seen the median overall survival (OS) for mCRC increase from 9 months to > 2 years. Data from trials integrating targeted therapies appear to indicate that not all have efficacy as single agents and the choice of chemotherapy used in combination with these agents may impact results. Ongoing research is leading to identification of new biomarkers of response, further defining the subpopulations who achieve greatest benefit. Hence optimizing treatment for this group of patients has become increasingly complex, requiring a multidisciplinary approach not only to identify those who are curable with resectable disease but also to determine when it is best to incorporate targeted drugs, with which chemotherapy, and in whom. Currently bevacizumab, cetuximab, and panitumumab are the only approved biologic agents for use in mCRC. In this article we discuss the evidence supporting the use of biologic agents with chemotherapy and suggested strategies for their integration into the treatment armamentarium of mCRC.

Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a phase 3 comparison of dose intensification wit

Publisher: Elsevier BV

Date: 05-2013

DOI: 10.1016/S0140-6736(13)60313-X

Patient selection and tolerability of high-dose methotrexate as central nervous system prophylaxis in diffuse large B-cell lymphoma.

Publisher: Springer Science and Business Media LLC

Date: 17-12-2019

DOI: 10.1007/S00280-019-04007-W

Abstract: Central nervous system (CNS) relapse in diffuse large B-cell lymphoma (DLBCL) is usually fatal. Risk stratification of patients has historically been poorly defined, and CNS prophylaxis with high-dose methotrexate (HDMTX) can be associated with multiple toxicities. The CNS International Prognostic Index (IPI) defines three patient risk groups for CNS disease. The aims of this study were to evaluate the toxicity of HDMTX and describe outcomes in HDMTX and non-HDMTX patients according to the CNS-IPI. 205 patients diagnosed with DLBCL between 2004 and 2014, initially treated with RCHOP-like chemotherapy and considered for HDMTX CNS prophylaxis were identified by pharmacy records at two teaching hospitals. Patient records were retrospectively reviewed for HDMTX toxicity, CNS-IPI calculation and CNS relapse. 28 patients with DLBCL were selected for two doses of HDMTX. Two of 28 patients received only one dose, and three had their second dose reduced due to renal impairment. 28% of patients experienced nephrotoxicity. 24 HDMTX and 122 non-HDMTX patients were evaluable for the CNS-IPI. No significant difference in the CNS-IPI distribution between the two groups was identified (p = 0.695). Five patients had CNS relapse, two who received HDMTX and three who did not. No significant difference in CNS relapse rate was identified between 24 HDMTX patients propensity-matched to 24 non-HDMTX patients. HDMTX was well-tolerated by patients. Application of the CNS-IPI identifies a different population of candidates for CNS prophylaxis compared to traditional criteria.

Single-agent activity of phosphatidylinositol 3-kinase inhibition with copanlisib in patients with molecularly defined relapsed or refractory diffuse large B-cell lymphoma.

Publisher: Springer Science and Business Media LLC

Date: 14-02-2020

DOI: 10.1038/S41375-020-0743-Y

Abstract: Patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) have adverse outcomes. We evaluated the efficacy and safety of the phosphatidylinositol 3-kinase inhibitor copanlisib in patients with relapsed/refractory DLBCL and assessed the relationship between efficacy and DLBCL cell of origin (COO activated B-cell like [ABC] and germinal center B-cell like [GCB]) and other biomarkers. The primary endpoint was objective response rate (ORR) in DLBCL COO subgroups (ABC, GCB, and unclassifiable) and by CD79B mutational status (NCT02391116). Sixty-seven patients received copanlisib (ABC DLBCL, n = 19 GCB DLBCL, n = 30 unclassifiable, n = 3 missing, n = 15). The ORR was 19.4% 31.6% and 13.3% in ABC and GCB DLBCL patients, respectively. ORR was 22.2%/20.0% for patients with/without CD79B mutations (wild type, n = 45 mutant, n = 9 missing, n = 13). Overall median progression-free survival and duration of response were 1.8 and 4.3 months, respectively. Adverse events included hypertension (40.3%), diarrhea (37.3%), and hyperglycemia (32.8%). Aberrations were detected in 338 genes, including BCL2 (53.7%) and MLL2 (53.7%). A 16-gene signature separating responders from nonresponders was identified. Copanlisib treatment demonstrated a manageable safety profile in patients with relapsed/refractory DLBCL and a numerically higher response rate in ABC vs. GCB DLBCL patients.

Rituximab, Gemcitabine, Cisplatin and Methylprednisolone (R‐GEM‐P) is an effective regimen in relapsed diffuse large B‐cell lymphoma

Publisher: Wiley

Date: 18-08-2014

DOI: 10.1111/EJH.12416

Abstract: Patients with relapsed diffuse large B-cell lymphoma (DLBCL) have a poor prognosis. Gemcitabine, methylprednisolone, cisplatin +/- rituximab (GEM-P+/-R) is a salvage regimen with limited overlap in toxicity with first-line therapy and short duration of inpatient delivery. We assessed the efficacy and safety of GEM-P+/-R in a retrospective single-centre analysis including patients meeting criteria of ≥ 18 yr of age, histologically proven DLBCL, treated between 2001 and 2011 in second-line with gemcitabine 1000 mg/m(2) day 1, 8 and 15, methylprednisolone 1000 mg day 1-5, cisplatin 100 mg/m(2) day 15 (replaced with carboplatin AUC5 if contraindication/toxicity) +/- rituximab 375 mg/m(2) day 1 and 15, every 28 d. Forty-five patients aged 25-74 received a median of three cycles of GEM-P+/-R 64% received rituximab. In 44 evaluable patients receiving GEM-P+/-R, overall response rate (ORR) was 48% in 28 evaluable patients treated with rituximab + GEM-P (R-GEM-P), ORR was 61%. With median follow-up of 50.5 months (95% CI: 28.3-72.7), 3-yr overall survival (OS) from start of GEM-P+/-R was 31.4% (95% CI: 16.5-46.3) in patients treated with R-GEM-P, 3-yr OS was 49.1% (95% CI: 28.7-69.5). Predominant grade ≥ 3 toxicities were haematological thrombocytopenia 69%, neutropenia 60% and febrile neutropenia 7%. R-GEM-P is a deliverable regimen with useful activity in second-line treatment of DLBCL. Our data suggest that rituximab should be given concurrently.

Simplified Geriatric Assessment in Older Patients With Diffuse Large B-Cell Lymphoma: The Prospective Elderly Project of the Fondazione Italiana Linfomi

Publisher: American Society of Clinical Oncology (ASCO)

Date: 10-04-2021

DOI: 10.1200/JCO.20.02465

Abstract: To prospectively validate the use of a simplified geriatric assessment (sGA) at diagnosis and to integrate it into a prognostic score for older patients with diffuse large B-cell lymphoma (DLBCL). We conducted the prospective Elderly Project study on patients with DLBCL older than 64 years who underwent our Fondazione Italiana Linfomi original geriatric assessment (oGA) (age, Cumulative Illness Rating Scale for Geriatrics, activities of daily living, and instrumental activities of daily living) before treatment. Treatment choice was left to the physician's discretion. The primary end point was overall survival (OS) (ClinicalTrials.gov identifier: NCT02364050 ). We analyzed 1,163 patients (median age 76 years), with a 3-year OS of 65% (95% CI, 62 to 68). Because at multivariate analysis on oGA, age 80 years retained an independent correlation with OS, we also developed a new, simplified version of the GA (sGA) that classifies patients as fit (55%), unfit (28%), and frail (18%) with significantly different 3-year OS of 75%, 58%, and 43%, respectively. The sGA groups, International Prognostic Index, and hemoglobin levels were independent predictors of OS and were used to build the Elderly Prognostic Index (EPI). Three risk groups were identified: low (23%), intermediate (48%), and high (29%), with an estimated 3-year OS of 87% (95% CI, 81 to 91), 69% (95% CI, 63 to 73), and 42% (95% CI, 36 to 49), respectively. The EPI was validated using an independent external series of 328 cases. The Elderly Project validates sGA as an objective tool to assess fitness status and defines the new EPI to predict OS of older patients with DLBCL.

High-Dose Methotrexate as CNS Prophylaxis in High-Risk Aggressive B-Cell Lymphoma

Publisher: American Society of Clinical Oncology (ASCO)

Date: 05-10-2023

DOI: 10.1200/JCO.23.00365

Chemoimmunotherapy may not be dead yet in chronic lymphocytic leukemia, but fludarabine plus cyclophosphamide plus rituximab is potentially facing life support

Publisher: American Society of Clinical Oncology (ASCO)

Date: 20-12-2017

DOI: 10.1200/JCO.2017.75.4721

Gastrointestinal Lymphoma

Publisher: Wiley

Date: 12-07-2012

DOI: 10.1002/9781118423318.CH10

Safety and efficacy of zanubrutinib in relapsed/refractory marginal zone lymphoma: final analysis of the MAGNOLIA study

Publisher: American Society of Hematology

Date: 08-09-2023

DOI: 10.1182/BLOODADVANCES.2023010668

Are we ready to restrict EGFR therapy to quadruple-negative colorectal cancer?

Publisher: Elsevier BV

Date: 11-2010

DOI: 10.1016/S1470-2045(10)70211-4

Australian experience with ibrutinib in patients with relapsed/refractory mantle cell lymphoma: a study from the Lymphoma and Related Diseases Registry

Publisher: Informa UK Limited

Date: 21-12-2022

DOI: 10.1080/10428194.2022.2157676

The unique entity of nodular lymphocyte-predominant Hodgkin lymphoma: current approaches to diagnosis and management

Publisher: Informa UK Limited

Date: 19-09-2011

DOI: 10.3109/10428194.2011.608455

Abstract: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare disease constituting only 3-8% of all Hodgkin lymphoma. It has a distinct histological and clinical presentation as well as significantly different natural history compared to the classical form of Hodgkin lymphoma. Presenting most often as early-stage disease, NLPHL is characterized by frequent relapses, but paradoxically an overall good prognosis. The approach to management should therefore reflect this pattern and focus on attaining prolonged remissions, with long-term follow-up paramount. Due to the rarity of the disease, few prospective data exist. Options for treatment include radiotherapy, chemotherapy or combined chemotherapy plus radiotherapy and targeted anti-CD20 antibody therapy, as well as observation in selected patients.

Central nervous system relapse of diffuse large B-cell lymphoma in the rituximab era: results of the UK NCRI R-CHOP-14 versus 21 trial

Publisher: Elsevier BV

Date: 10-2017

DOI: 10.1093/ANNONC/MDX353

The MAGNOLIA Trial: Zanubrutinib, a Next-Generation Bruton Tyrosine Kinase Inhibitor, Demonstrates Safety and Efficacy in Relapsed/Refractory Marginal Zone Lymphoma

Publisher: American Association for Cancer Research (AACR)

Date: 15-09-2021

DOI: 10.1158/1078-0432.CCR-21-1704

Abstract: Marginal zone lymphoma (MZL) is an uncommon non–Hodgkin lymphoma with malignant cells that exhibit a consistent dependency on B-cell receptor signaling. We evaluated the efficacy and safety of zanubrutinib, a next-generation selective Bruton tyrosine kinase inhibitor, in patients with relapsed/refractory (R/R) MZL. Patients with R/R MZL were enrolled in the phase II MAGNOLIA (BGB-3111–214) study. The primary endpoint was overall response rate (ORR) as determined by an independent review committee (IRC) based on the Lugano 2014 classification. Sixty-eight patients were enrolled. After a median follow-up of 15.7 months (range, 1.6 to 21.9 months), the IRC-assessed ORR was 68.2% and complete response (CR) was 25.8%. The ORR by investigator assessment was 74.2%, and the CR rate was 25.8%. The median duration of response (DOR) and median progression-free survival (PFS) by independent review was not reached. The IRC-assessed DOR rate at 12 months was 93.0%, and IRC-assessed PFS rate was 82.5% at both 12 and 15 months. Treatment was well tolerated with the majority of adverse events (AE) being grade 1 or 2. The most common AEs were diarrhea (22.1%), contusion (20.6%), and constipation (14.7%). Atrial fibrillation/flutter was reported in 2 patients 1 patient had grade 3 hypertension. No patient experienced major hemorrhage. In total, 4 patients discontinued treatment due to AEs, none of which were considered treatment-related by the investigators. Zanubrutinib demonstrated high ORR and CR rate with durable disease control and a favorable safety profile in patients with R/R MZL.

Longitudinal exploration of cancer-related cognitive impairment in patients with newly diagnosed aggressive lymphoma: protocol for a feasibility study

Publisher: BMJ

Date: 09-2020

DOI: 10.1136/BMJOPEN-2020-038312

Abstract: Cancer-related cognitive impairment (CRCI) is a distressing and disabling side-effect of cancer treatments affecting up to 75% of patients. For some patients, their cognitive impairment may be transient, but for a subgroup, these symptoms can be long-standing and have a major impact on the quality of life. This paper describes the protocol for a study: (1) to assess the feasibility of collecting longitudinal data on cognition via self-report, neuropsychological testing, peripheral markers of inflammation and neuroimaging and (2) to explore and describe patterns of cancer-related cognitive impairment over the course of treatment and recovery in patients with newly diagnosed, aggressive lymphoma undergoing standard therapy with curative intent. This is a prospective, longitudinal, feasibility study in which 30 newly diagnosed, treatment-naive patients with aggressive lymphoma will be recruited over a 12-month period. Patients will complete comprehensive assessments at three time points: baseline (time 1, pre-treatment) and two post-baseline follow-up assessments (time 2, mid-treatment and time 3, 6–8 weeks post-treatment completion). All patients will be assessed for self-reported cognitive difficulties and objective cognitive function using Stroop Colour and Word, Trail Making Test Part A and B, Hopkins Verbal Learning Test-Revised, Controlled Oral Word Association and Digit Span. Blood cell-based inflammatory markers and neuroimaging including a positron emission tomography (PET) with 18 F-labelled fluoro-2-deoxyglucose ( 18 F-FDG) and CT ( 18 F-FDG-PET/CT) and a MRI will explore potential inflammatory and neuroanatomical or functional mechanisms and biomarkers related to CRCI. The primary intent of analysis will be to assess the feasibility of collecting longitudinal data on cognition using subjective reports and objective tasks from patients during treatment and recovery for lymphoma. These data will inform the design of a larger-scale investigation into the patterns of cognitive change over the course of treatment and recovery, adding to an underexplored area of cancer survivorship research. Ethical approval has been granted by Austin Health Human Rights Ethics Committee (HREC) in Victoria Australia. Peer reviewed publications and conference presentations will report the findings of this novel study. Australian New Zealand Clinical Trials Registry (ACTRN12619001649101).

Outcomes of stage I/II follicular lymphoma in the PET era: an international study from the Australian Lymphoma Alliance

Publisher: American Society of Hematology

Date: 30-09-2019

DOI: 10.1182/BLOODADVANCES.2019000458

Abstract: Practices in early-stage FL are variable and include radiation alone, systemic therapy, CMT, or observation. Each practice resulted in similar excellent outcomes randomized trials are required to determine the optimal treatment.

Prognostication of diffuse large B-cell lymphoma in the molecular era: moving beyond the IPI

Publisher: Elsevier BV

Date: 09-2018

DOI: 10.1016/J.BLRE.2018.03.005

Abstract: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with variable outcomes. Despite the majority of patients being cured with combination chemoimmunotherapy, up to 30% eventually succumb to the disease. Until recently, baseline prognostic assessment has centred on the International Prognostic Index (IPI), although this index is yet to impact strongly on treatment choice. Molecular features such as cell of origin, MYC and BCL-2 genetic alterations and protein overexpression were identified over a decade ago, yet their prognostic value is still not fully elucidated. Adding complexity are the plethora of new clinical, biological and molecular prognostic markers described in the recent literature, most of which lack independent validation, likely act as surrogate markers for those already in common use and have yet to substantially impact on therapeutic decision making. This review comprehensively assesses the value of in idual prognostic markers in the clinical setting and their potential to predict response to novel agents, and ways to optimise their use in future research.

Is upfront escalated BEACOPP for advanced Hodgkin lymphoma becoming a distant memory?

Publisher: American Society of Clinical Oncology (ASCO)

Date: 20-01-2017

DOI: 10.1200/JCO.2016.68.2047

Urine cultures at the onset of febrile neutropenia rarely impact antibiotic management in asymptomatic adult cancer patients

Publisher: Springer Science and Business Media LLC

Date: 27-09-2018

DOI: 10.1007/S00520-018-4476-7

Abstract: There is a paucity of data regarding the utility of routine urine cultures in adults with febrile neutropenia (FN) without urinary symptoms receiving protocolised antibiotics. This is reflected by inconsistent recommendations in international and regional FN guidelines. We addressed this issue by retrospectively reviewing the impact of routine urine cultures on antibiotic management in haematology cancer inpatients at a tertiary hospital. All haematology inpatients over a 5-year period (2011-2015) were retrospectively reviewed for episodes of FN (neutrophil count < 0.5 × 10 Four hundred and thirty-three episodes of FN were identified in 317 patients. Urine cultures were performed in 362 (84%) episodes. Cultures were positive in 9 of 48 (19%) symptomatic episodes versus 8 of 314 (2.5%) asymptomatic episodes (RR = 7.4, p < 0.0001). A change in antibiotic management due a positive urine culture occurred in only 5 episodes (1.4%): 3 of 48 (6.3%) symptomatic and 2 of 314 (0.6%) asymptomatic episodes respectively (RR = 9.8, p = 0.01). Routine urine cultures in FN patients without urinary symptoms who are already receiving protocolised broad spectrum antibiotics rarely impact subsequent antibiotic management.

Limited utility of routine chest X‐ray in initial evaluation of neutropenic fever in patients with haematological diseases undergoing chemotherapy

Publisher: Wiley

Date: 05-2018

DOI: 10.1111/IMJ.13712

Abstract: Routine chest X-ray (CXR) is recommended for neutropenic fever (NF) management however its role is relatively understudied in haematology patients. To investigate the utility of CXR in the diagnosis and management of patients with haematological conditions complicated by NF. Retrospective, single-centre analysis of haematology patients admitted with NF between January 2011 and December 2015. Baseline demographics, treatment details and outcomes were collected from electronic patient records. CXR underwent independent radiology review. Primary endpoints were a proportion of NF episodes in which CXR detected a probable chest infection in the absence of respiratory symptoms/signs and/or resulted in a change in antibiotic management. Four hundred and thirty-five episodes were identified CXR was performed in 75% of patients (65% within 2 days of NF). In 4 of 164 (2.4%) asymptomatic patients, CXR was consistent with infection, in contrast to 19 of 119 (16%) patients with clinical signs of respiratory infection. Only 3 of 283 (1.1%) CXR resulted in a change to antibiotics. CXR consistent with infection was not associated with increased mortality or increased admission length, although there was an association with intensive care unit admission (odds ratios: 7.61, 95% confidence interval: 2.04-28.31). In haematology patients with NF, CXR rarely detected chest infection or changed management in patients with no respiratory symptoms or signs. CXR in our institution is no longer part of routine assessment of NF in the absence of these features.

Inferior vena caval leiomyosarcoma in a patient with past bilateral retinoblastoma

Publisher: Wiley

Date: 09-2008

DOI: 10.1111/J.1743-7563.2008.00183.X

Durable remission of both multicentric Castleman's disease and Kaposi's sarcoma with valganciclovir, rituximab and liposomal doxorubicin in an HHV-8-positive, HIV-negative patient

Publisher: Hindawi Limited

Date: 28-10-2017

DOI: 10.1111/JCPT.12472

Abstract: Human herpesvirus-8 (HHV-8)-positive, HIV-negative multicentric Castleman's disease is a rare lymphoproliferative disorder with no standardized treatment. Concurrent Kaposi's sarcoma, another HHV-8-related disease, is uncommon in HIV-negative patients. The role of antiviral therapy and rituximab in HIV-negative patients is not well established. We report a case of a 5-year, durable remission of HHV-8-positive, HIV-negative comorbid multicentric Castleman's disease and Kaposi's sarcoma treated with long-term valganciclovir, following initial rituximab and liposomal doxorubicin. Currently, there is no defined role for antiviral therapy in the treatment of HIV-negative HHV-8-positive multicentric Castleman's disease and Kaposi's sarcoma. Ganciclovir followed by indefinite, continuous valganciclovir is thought to have contributed significantly to the durable response in this case.

Efficacy and toxicity of PACEBOM chemotherapy in relapsed/refractory aggressive lymphoma in the rituximab era

Publisher: Wiley

Date: 22-12-2017

DOI: 10.1111/AJCO.12611

Abstract: Relapsed/refractory (R/R) aggressive lymphoma outcomes are poor. There is no standard treatment. PACEBOM (prednisolone, doxorubicin, cyclophosphamide, etoposide, bleomycin, vincristine and methotrexate) has shown efficacy for several lymphoma subtypes in published reports. We evaluate PACEBOM+/-rituximab for R/R aggressive lymphomas in this millennium. In this retrospective, single-center study, R/R aggressive lymphoma patients who received PACEBOM or its derivatives were identified from the pharmacy database. Demographic, treatment, toxicity and survival data were collected. A total of 37 eligible patients were identified. Histological subtypes included 20 Diffuse Large B-Cell Lymphoma (DLBCL), 10 T-Cell Lymphoma (TCL) and 7 Hodgkin lymphoma. All DLBCL patients had received prior rituximab. Thirty-one (84%) received second-line PACEBOM. Median number of cycles was six (1-6). Eighteen out of 20 B-cell lymphoma patients received R-PACEBOM. Overall response rate was 65%, 70% and 71% in patients with DLBCL, TCL and Hodgkin lymphoma respectively. Thirteen patients underwent autologous stem cell transplant post-PACEBOM. Median follow-up was 49 months (3-201). Most common grade 3-4 toxicities were neutropenia (46%), anemia (24%) and thrombocytopenia (16%). No additional toxicity was seen in patients who received rituximab. In this cohort, PACEBOM is active in R/R aggressive lymphoma with manageable toxicity and can be safely combined with rituximab. Outcomes were similar to reports of other salvage regimens. PACEBOM remains a suitable option for R/R aggressive lymphoma, in patients exposed to prior rituximab and those planned for autologous stem cell transplant.

Women in Lymphoma: A 4‐year journey in promoting gender equity

Publisher: Wiley

Date: 25-05-2023

DOI: 10.1002/HON.3183

Caution in the Use of Immunohistochemistry for Determination of Cell of Origin in Diffuse Large B-Cell Lymphoma

Publisher: American Society of Clinical Oncology (ASCO)

Date: 10-2015

DOI: 10.1200/JCO.2014.60.6731

Ibrutinib for central nervous system lymphoma: the Australasian Lymphoma Alliance/MD Anderson Cancer Center experience

Publisher: Wiley

Date: 16-07-2020

DOI: 10.1111/BJH.16946

Limited-stage diffuse large B-cell lymphoma

Publisher: American Society of Hematology

Date: 10-02-2022

DOI: 10.1182/BLOOD.2021013998

Abstract: Diffuse large B-cell lymphoma (DLBCL), the most common lymphoma subtype, is localized in 25% to 30% of patients. Prognosis in patients with limited-stage DLBCL (LS-DLBCL) is excellent with 10-year overall survival of at least 70% to 80%. Improved insights into the disease biology, the availability of positron-emission tomography (PET) scans, and recent dedicated clinical trials within this unique population have led to evolving treatment paradigms. However, no standard definition of LS-DLBCL exists, and although generally defined as Ann Arbor stages I to II disease with largest mass size & cm in diameter, variations across studies cause challenges in interpretation. Similar to advanced-stage disease, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) immunochemotherapy forms the basis of treatment, with combined modality therapy including 3 cycles of systemic treatment and involved-site radiation therapy being a predominant historical standard. Yet the well-described continuous risk of relapse beyond 5 years and established late complications of radiotherapy have challenged previous strategies. More rigorous baseline staging and response assessment with PET may improve decision making. Recent clinical studies have focused on minimizing toxicities while maximizing disease outcomes using strategies such as abbreviated immunochemotherapy alone and PET-adapted radiotherapy delivery. This comprehensive review provides an update of recent literature with recommendations for integration into clinical practice for LS-DLBCL patients.

Outcome of elderly patients with diffuse large B-cell lymphoma treated with R-CHOP: results from the UK NCRI R-CHOP14v21 trial with combined analysis of molecular characteristics with the DSHNHL RICOV

Publisher: Elsevier BV

Date: 07-2017

DOI: 10.1093/ANNONC/MDX128

Predictive and Prognostic Biomarkers for Targeted Therapy in Metastatic Colorectal Cancer

Publisher: Elsevier BV

Date: 12-2010

DOI: 10.3816/CCC.2010.N.040

Flexible sigmoidoscopy—valuable in colorectal cancer

Publisher: Springer Science and Business Media LLC

Date: 09-2010

DOI: 10.1038/NRCLINONC.2010.102

Improving outcomes for patients with lymphoma: Design and development of the Australian Lymphoma and Related Diseases Registry

Publisher: Research Square Platform LLC

Date: 22-03-2022

DOI: 10.21203/RS.3.RS-1370973/V1

Abstract: Background Lymphoma is a malignancy of lymphocytes and lymphoid tissues comprising a heterogeneous group of diseases, with up to 80 entities now described. Lymphoma is the 6 th most common cancer in Australia, affecting patients of all ages, with rising incidence rates. With the proliferation of efficacious novel agents, therapeutic strategies are increasingly erse and survival is improving. There is a clear need for contemporary robust and detailed data on diagnostic, investigational and management strategies for this disease in Australia, New Zealand and worldwide, to inform and benchmark local and international standards of care. Clinical quality registries can provide these data, and support development of strategies to address variations in management, including serving as platforms for clinical trials and research. The Lymphoma and Related Diseases Registry (LaRDR) was developed to capture details of patient demographics, disease characteristics, and management throughout their disease course and therapy and to develop outcome benchmarks nationally and internationally for lymphoma. This report describes the aims, development and implementation of the LaRDR, as well as challenges addressed in the process. Methods The LaRDR was established in 2016 as a multicentre, collaborative project at sites across Australia with a secure online database which collects prospective data on patients with a new diagnosis of lymphoma or chronic lymphocytic leukaemia (CLL). LaRDR development required multidisciplinary participation including specialist haematology, information technology, and biostatistical support, as well as secure funding. Here we describe the database development, data entry, ethics approval process, registry governance and support for participating sites and the coordinating centre. Results To date more than 4,700 patients have been enrolled from 27 sites. Multiple challenges arose during the development, which we describe, along with approaches used to overcome them. Several confirmed international collaborations are now in place, and the registry is providing valuable data for clinicians, researchers, industry and government, including through presentations of results at major national and international conferences. Conclusion Challenges in establishing the LaRDR have been successfully overcome and the registry is now a valuable resource for lymphoma clinicians, researchers, health economists and others in Australia and globally.

Cardiotoxicity in Patients Treated With Bevacizumab Is Potentially Reversible

Publisher: American Society of Clinical Oncology (ASCO)

Date: 20-06-2011

DOI: 10.1200/JCO.2011.35.5008

Reply to M. Mohiuddin et al

Publisher: American Society of Clinical Oncology (ASCO)

Date: 07-2011

DOI: 10.1200/JCO.2011.36.2186

Rechallenge with Platinum plus Fluoropyrimidine +/– Epirubicin in Patients with Oesophagogastric Cancer

Publisher: S. Karger AG

Date: 2010

DOI: 10.1159/000322114

Abstract: i Purpose: /i There is no standard second-line therapy for patients with oesophagogastric cancer who progress following first-line chemotherapy for advanced disease or relapse following radical multi-modality therapy. The aim of this retrospective study was to evaluate survival following rechallenge with platinum plus fluoropyrimidine (PF) +/– epirubicin. i Methods: /i Patients treated with PF +/– epirubicin for oesophagogastric cancer at our institution were identified from the electronic prescribing database. Patients rechallenged with PF +/– epirubicin months after completing initial chemotherapy were eligible. Primary endpoint was survival, calculated from day 1 of rechallenge treatment to date of death or last follow-up. Secondary endpoints were progression-free survival and response rate to PF-based re-challenge. i Results: /i Between 2000 and 2008, 950 patients treated with PF +/– epirubicin for oesophagogastric cancer were identified. 298 patients progressed or relapsed months after completing chemotherapy, of whom 106 patients were rechallenged with PF-based chemotherapy. Median progression-free survival and overall survival were 5.1 and 10 months, respectively, from date of rechallenge for patients treated with initial radical intent and 3.9 and 6.6 months, respectively, in patients treated with palliative intent from diagnosis. In a survival analysis, no significant prognostic factors were identified. i Conclusion: /i Selected patients with oesophagogastric cancer who relapse or progress months after initial treatment with PF +/– epirubicin may benefit from re-introduction of PF-based chemotherapy.

A consensus statement on the use of biosimilar medicines in hematology in Australia

Publisher: Wiley

Date: 14-04-2020

DOI: 10.1111/AJCO.13337

Exploration of motivation to participate in a study of cancer-related cognitive impairment among patients with newly diagnosed aggressive lymphoma: a qualitative sub-study

Publisher: Springer Science and Business Media LLC

Date: 08-09-2021

DOI: 10.1007/S00520-021-06527-9

Abstract: Cancer-related cognitive impairment (CRCI) is a recognised adverse consequence of cancer and its treatment. This qualitative sub-study was undertaken as part of a larger prospective longitudinal study in which recruitment and retention were very high. The aim was to gain an understanding of participants reasons for ongoing participation, at a time of heightened stress related to a new diagnosis of aggressive lymphoma and the rapid commencement of treatment. This qualitative descriptive sub-study included semi-structured interviews with twenty-seven participants. Interviews were recorded and transcribed, and a thematic descriptive approach was used to analyse the data. Twenty-seven interviews were completed. Four themes described participants’ motivation to consent and continue with the study. These included ease of participation, personal values, self-help and valued additional support. Participants understood the requirements of the study, and data collection occurring during hospital visits was perceived to be convenient. Interviewees confirmed that the study fulfilled desire to “help others”. Although testing was intense and challenging, it provided feedback on current functioning and was described by some as a “welcome distraction” and enjoyable. Finally, interaction with the study nurse was perceived as an additional beneficial oversight and support. Achieving sustained participation in a prospective study with patients undergoing treatment is facilitated where the logistical demands of data collection are minimised a clinician from the service is included the tasks are seen as inherently interesting and care is taken to provide empathic support throughout. Australian New Zealand Clinical Trials Registry ACTRN12619001649101

SAFETY ANALYSIS OF AUSTRALASIAN LEUKAEMIA & LYMPHOMA GROUP NHL29: A PHASE II STUDY OF IBRUTINIB, RITUXIMAB AND MINI-CHOP IN VERY ELDERLY PATIENTS WITH NEWLY DIAGNOSED DLBCL

Publisher: Wiley

Date: 06-2019

DOI: 10.1002/HON.63_2630

Integrated clinical and genomic evaluation of guadecitabine (SGI-110) in peripheral T-cell lymphoma

Publisher: Springer Science and Business Media LLC

Date: 22-04-2022

DOI: 10.1038/S41375-022-01571-8

Abstract: Peripheral T-cell lymphoma (PTCL) is a rare, heterogenous malignancy with dismal outcomes at relapse. Hypomethylating agents (HMA) have an emerging role in PTCL, supported by shared mutations with myelodysplasia (MDS). Response rates to azacitidine in PTCL of follicular helper cell origin are promising. Guadecitabine is a decitabine analogue with efficacy in MDS. In this phase II, single-arm trial, PTCL patients received guadecitabine on days 1–5 of 28-day cycles. Primary end points were overall response rate (ORR) and safety. Translational sub-studies included cell free plasma DNA sequencing and functional genomic screening using an epigenetically-targeted CRISPR/Cas9 library to identify response predictors. Among 20 predominantly relapsed/refractory patients, the ORR was 40% (10% complete responses). Most frequent grade 3-4 adverse events were neutropenia and thrombocytopenia. At 10 months median follow-up, median progression free survival (PFS) and overall survival (OS) were 2.9 and 10.4 months respectively. RHOA G17V mutations associated with improved PFS (median 5.47 vs . 1.35 months Wilcoxon p = 0.02, Log-Rank p = 0.06). 4/7 patients with TP53 variants responded. Deletion of the histone methyltransferase SETD2 sensitised to HMA but TET2 deletion did not. Guadecitabine conveyed an acceptable ORR and toxicity profile decitabine analogues may provide a backbone for future combinatorial regimens co-targeting histone methyltransferases.

Increased STAT expression in Reed–Sternberg cells as a potential positive prognostication biomarker in Hodgkin lymphoma

Publisher: Elsevier BV

Date: 08-2023

DOI: 10.1016/J.PATHOL.2023.02.007

Correction to: Exploration of motivation to participate in a study of cancer-related cognitive impairment among patients with newly diagnosed aggressive lymphoma: a qualitative sub-study

Publisher: Springer Science and Business Media LLC

Date: 18-09-2021

DOI: 10.1007/S00520-021-06562-6

Routine blood tests in asymptomatic patients with indolent lymphoma have limited ability to detect clinically significant disease progression

Publisher: American Society of Clinical Oncology (ASCO)

Date: 11-2020

DOI: 10.1200/JOP.19.00771

Abstract: Patients with indolent non-Hodgkin lymphoma (iNHL) undergo regular active surveillance in between treatment periods to detect disease relapse or progression. As part of surveillance, international guidelines recommend regular routine blood testing, which is based on consensus rather than evidence of utility. We conducted a retrospective analysis of all patients older than age 16 years diagnosed with grade 1-3A follicular or marginal zone lymphoma between 2008 and 2017 from 2 Australian cancer centers to assess the utility of full blood examination, lactate dehydrogenase, and β 2 -microglobulin in detecting progression events, defined as either disease relapse or progression of disease. One hundred eighty patients attended 1,757 outpatient appointments (median follow-up, 36 months). Routine blood tests (RBTs) were performed before 83% of appointments. Seventy-four progression events occurred in 62 patients. Only 2 events (3%) were detected by RBTs alone, both of which occurred in treatment-naïve patients who subsequently developed symptoms within 3 weeks. The remainder of progression events were suspected clinically (88%) or detected by imaging (9%). RBT results were frequently abnormal in asymptomatic patients (19%), with abnormal results leading to either additional investigations or an increased surveillance frequency in 8% of cases. The overall sensitivity and positive predictive value of abnormal RBT results in detecting progression events were 39% and 9%, respectively. RBTs have poor performance characteristics and rarely detect clinically significant disease progression or relapse in asymptomatic patients with iNHL.

An abscopal effect may augment PD-1 inhibition in refractory classical Hodgkin lymphoma

Publisher: Informa UK Limited

Date: 23-03-2018

DOI: 10.1080/10428194.2018.1452217

EBV-associated primary CNS lymphoma occurring after immunosuppression is a distinct immunobiological entity.

Publisher: American Society of Hematology

Date: 18-03-2021

DOI: 10.1182/BLOOD.2020008520

Abstract: Primary central nervous system lymphoma (PCNSL) is confined to the brain, eyes, and cerebrospinal fluid without evidence of systemic spread. Rarely, PCNSL occurs in the context of immunosuppression (eg, posttransplant lymphoproliferative disorders or HIV [AIDS-related PCNSL]). These cases are poorly characterized, have dismal outcome, and are typically Epstein-Barr virus (EBV)-associated (ie, tissue-positive). We used targeted sequencing and digital multiplex gene expression to compare the genetic landscape and tumor microenvironment (TME) of 91 PCNSL tissues all with diffuse large B-cell lymphoma histology. Forty-seven were EBV tissue-negative: 45 EBV− HIV− PCNSL and 2 EBV− HIV+ PCNSL and 44 were EBV tissue-positive: 23 EBV+ HIV+ PCNSL and 21 EBV+ HIV− PCNSL. As with prior studies, EBV− HIV− PCNSL had frequent MYD88, CD79B, and PIM1 mutations, and enrichment for the activated B-cell (ABC) cell-of-origin subtype. In contrast, these mutations were absent in all EBV tissue-positive cases and ABC frequency was low. Furthermore, copy number loss in HLA class I/II and antigen-presenting rocessing genes were rarely observed, indicating retained antigen presentation. To counter this, EBV+ HIV− PCNSL had a tolerogenic TME with elevated macrophage and immune-checkpoint gene expression, whereas AIDS-related PCNSL had low CD4 gene counts. EBV-associated PCNSL in the immunosuppressed is immunobiologically distinct from EBV− HIV− PCNSL, and, despite expressing an immunogenic virus, retains the ability to present EBV antigens. Results provide a framework for targeted treatment.

A Randomized Phase II/III Study of Dalotuzumab in Combination With Cetuximab and Irinotecan in Chemorefractory,KRASWild-Type, Metastatic Colorectal Cancer

Publisher: Oxford University Press (OUP)

Date: 23-09-2015

DOI: 10.1093/JNCI/DJV258

Abstract: Insulin-like growth factor type 1 receptor (IGF-1R) mediates resistance to epidermal growth factor receptor (EGFR) inhibition and may represent a therapeutic target. We conducted a multicenter, randomized, double blind, phase II/III trial of dalotuzumab, an anti-IGF-1R monoclonal antibody, with standard therapy in chemo-refractory, KRAS wild-type metastatic colorectal cancer. Eligible patients were randomly assigned to dalotuzumab 10mg/kg weekly (arm A), dalotuzumab 7.5mg/kg every alternate week (arm B), or placebo (arm C) in combination with cetuximab and irinotecan. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints included exploratory biomarker analyses. All statistical tests were two-sided. The trial was prematurely discontinued for futility after 344 eligible KRAS wild-type patients were included in the primary efficacy population (arm A = 116, arm B = 117, arm C = 111). Median PFS was 3.9 months in arm A (hazard ratio [HR] = 1.33, 95% confidence interval [CI] = 0.98 to 1.83, P = .07) and 5.4 months in arm B (HR = 1.13, 95% CI = 0.83 to 1.55, P = .44) compared with 5.6 months in arm C. Median OS was 10.8 months in arm A (HR = 1.41, 95% CI = 0.99 to 2.00, P = .06) and 11.6 months in arm B (HR = 1.26, 95% CI = 0.89 to 1.79, P = .18) compared with 14.0 months in arm C. Grade 3 or higher asthenia and hyperglycaemia occurred more frequently with dalotuzumab compared with placebo. In exploratory biomarker analyses, patients with high IGF-1 mRNA tumors in arm A had numerically better PFS (5.6 vs 3.6 months, HR = 0.59, 95% CI = 0.28 to 1.23, P = .16) and OS (17.9 vs 9.4 months, HR = 0.67, 95% CI = 0.31 to 1.45, P = .31) compared with those with high IGF-1 mRNA tumors in arm C. In contrast, in arm C high IGF-1 mRNA expression predicted lower response rate (17.6% vs 37.3%, P = .04), shorter PFS (3.6 vs 6.6 months, HR = 2.15, 95% CI = 1.15 to 4.02, P = .02), and shorter OS (9.4 vs 15.5 months, HR = 2.42, 95% CI = 1.21 to 4.82, P = .01). Adding dalotuzumab to irinotecan and cetuximab was feasible but did not improve survival outcome. IGF-1R ligands are promising biomarkers for differential response to anti-EGFR and anti-IGF-1R therapies.

Diagnostic medical radiation exposure in surveillance of aggressive lymphoma: Clinical trial design should reflect clinical practice

Publisher: American Society of Clinical Oncology (ASCO)

Date: 04-2015

DOI: 10.1200/JCO.2014.60.0486

Neoadjuvant Chemotherapy Alone for Early-Stage Rectal Cancer: An Evolving Paradigm?

Publisher: Elsevier BV

Date: 07-2011

DOI: 10.1016/J.SEMRADONC.2011.02.005

Abstract: Current management of early-stage rectal cancer comprises combinations of surgery, radiotherapy, and chemotherapy, with the presence or absence of several validated high-risk features determining which treatment modalities will be used and the order of administration. In high-risk in iduals, most centers have adopted neoadjuvant combined chemotherapy and radiotherapy followed by surgery as the initial approach. However, long-term toxicity, limited survival gains, and high rates of distant failure have called this approach into question, with early data suggesting that neoadjuvant chemotherapy alone may be feasible in selected patient groups. This review discusses the current data and feasibility of managing early stage rectal cancer with neoadjuvant chemotherapy before surgical resection.

Dose-adjusted EPOCH-R therapy in MYC-rearranged diffuse large B-cell lymphoma: not yet the standard of care

Publisher: Elsevier BV

Date: 03-2019

DOI: 10.1016/S2352-3026(19)30013-4

CHOP versus GEM-P in previously untreated patients with peripheral T-cell lymphoma (CHEMO-T): a phase 2, multicentre, randomised, open-label trial

Publisher: Elsevier BV

Date: 05-2018

DOI: 10.1016/S2352-3026(18)30039-5

Caution in Expanding the Use of Abbreviated R-CHOP to Poor-Risk Limited-Stage DLBCL

Publisher: American Society of Clinical Oncology (ASCO)

Date: 10-12-2020

DOI: 10.1200/JCO.20.02301

Diagnosis, management and follow up of peripheral T‐cell lymphomas: a consensus practice statement from the Australasian Lymphoma Alliance

Publisher: Wiley

Date: 10-2022

DOI: 10.1111/IMJ.15595

Abstract: Peripheral T‐cell lymphomas (PTCL) represent a heterogeneous disease group accounting for 10% of non‐Hodgkin lymphomas. PTCL patients have typically poorer outcomes compared with aggressive B‐cell lymphomas. However, such outcomes are heavily dependent on subtype. Although anthracycline‐based regimens such as cyclophosphamide, doxorubicin, vincristine and prednisone remain the standard first‐line treatment for most aggressive PTCL, there are important variations including incorporation of novel agents, use of radiotherapy and judicious consideration of stem cell transplantation. Relapsed or refractory disease represents a significant area of unmet need where chemotherapy intensification has limited efficacy and novel agents such as brentuximab vedotin and pralatrexate provide additional opportunities for attainment of remission and potential stem cell transplant. In the future, pre‐therapy prognostic biomarkers including genomic characterisation, may aid in risk stratification and help guide initial patient management to improve survival. There is an urgent need to understand better the pathogenesis of PTCL to facilitate novel drug combinatorial approaches to improve survival. This position statement represents an evidence‐based synthesis of the literature for application in Australian and New Zealand practice.

Pralatrexate in relapsed/refractory T-cell lymphoma: a retrospective multicenter study

Publisher: Informa UK Limited

Date: 07-10-2020

DOI: 10.1080/10428194.2020.1827241

The Advanced-Stage Hodgkin Lymphoma International Prognostic Index: Development and Validation of a Clinical Prediction Model From the HoLISTIC Consortium

Publisher: American Society of Clinical Oncology (ASCO)

Date: 10-04-2023

DOI: 10.1200/JCO.22.02473

Abstract: The International Prognostic Score (IPS) has been used in classic Hodgkin lymphoma (cHL) for 25 years. However, analyses have documented suboptimal performance of the IPS among contemporarily treated patients. Harnessing multisource in idual patient data from the Hodgkin Lymphoma International Study for In idual Care consortium, we developed and validated a modern clinical prediction model. Model development via Transparent Reporting of a multivariable prediction model for In idual Prognosis Or Diagnosis guidelines was performed on 4,022 patients with newly diagnosed advanced-stage adult cHL from eight international phase III clinical trials, conducted from 1996 to 2014. External validation was performed on 1,431 contemporaneously treated patients from four real-world cHL registries. To consider association over a full range of continuous variables, we evaluated piecewise linear splines for potential nonlinear relationships. Five-year progression-free survival (PFS) and overall survival (OS) were estimated using Cox proportional hazard models. The median age in the development cohort was 33 (18-65) years nodular sclerosis was the most common histology. Kaplan-Meier estimators were 0.77 for 5-year PFS and 0.92 for 5-year OS. Significant predictor variables included age, sex, stage, bulk, absolute lymphocyte count, hemoglobin, and albumin, with slight variation for PFS versus OS. Moreover, age and absolute lymphocyte count yielded nonlinear relationships with outcomes. Optimism-corrected c-statistics in the development model for 5-year PFS and OS were 0.590 and 0.720, respectively. There was good discrimination and calibration in external validation and consistent performance in internal-external validation. Compared with the IPS, there was superior discrimination for OS and enhanced calibration for PFS and OS. We rigorously developed and externally validated a clinical prediction model in 5,000 patients with advanced-stage cHL. Furthermore, we identified several novel nonlinear relationships and improved the prediction of patient outcomes. An online calculator was created for in idualized point-of-care use.

Outcomes in grade 3B follicular lymphoma: an international study led by the Australasian Lymphoma Alliance

Publisher: Ferrata Storti Foundation (Haematologica)

Date: 23-02-2023

DOI: 10.3324/HAEMATOL.2022.281375

Abstract: Grade (G) 3B follicular lymphoma (FL) is a rare FL subtype which exists on a histological continuum between ‘low-grade’ (Grade 1, 2 and 3A FL) and diffuse large B-cell lymphoma (DLBCL) appearing to share features with each. Clinical characteristics and outcomes are poorly understood due to lack of adequate representation in prospective trials and large-scale analyses. We analyzed 157 G3BFL cases from 18 international centers, and two comparator groups G3AFL (n=302) and DLBCL (n=548). Composite histology with DLBCL or low-grade FL occurred in approximately half of G3BFL cases. With median 5 years follow-up, G3BFL overall (OS P

Programmed cell death-1 inhibition in lymphoma.

Publisher: Elsevier BV

Date: 05-2015

DOI: 10.1016/S1470-2045(15)70103-8

ASPECCT: panitumumab versus cetuximab for colorectal cancer.

Publisher: Elsevier BV

Date: 07-2014

DOI: 10.1016/S1470-2045(14)70269-4

Use of Ultrasonography Facilitates Noninvasive Evaluation of Lymphadenopathy in a Lymph Node Diagnostic Clinic

Publisher: Elsevier BV

Date: 02-2021

DOI: 10.1016/J.CLML.2020.09.012

Abstract: Prompt and accurate diagnosis of lymphadenopathy is important, yet there is wide variability in clinical approach and referral patterns, leading to unnecessary investigations and delays in diagnosis. To address this, a lymph node diagnostic clinic (LNDC) was established at our tertiary referral center. We retrospectively analyzed data from 320 consecutive patients referred to the LNDC from March 2008 to March 2020, to describe their management and outcomes. The most common diagnoses were reactive (57%) and malignant lymphadenopathy (28%). In those with reactive lymphadenopathy, 33% did not undergo further investigations, 37% underwent imaging only, and 29% underwent biopsy. For malignant lymphadenopathy, diagnosis was made at a median (interquartile range) of 9 (6-16) days from first LNDC review, with the decision to biopsy made at the first LNDC review in 95% of cases. Clinical features significantly associated with malignancy included age > 45, B symptoms, history of malignancy, and lymphadenopathy that was ≥ 2 cm, in multiple regions, bilateral, multiple nodes, or supraclavicular. At least 3 of these features were present in 88% of patients with malignant lymphadenopathy. Ultrasound had a sensitivity of 98% and negative predictive value of 97% for detecting malignant lymphadenopathy. A dedicated LNDC in a tertiary referral center facilitates rapid assessment and diagnosis of lymphadenopathy through a risk-stratified model of management. Ultrasonography, as well as the presence of defined clinical risk factors, were most useful to differentiate benign from malignant lymphadenopathy.

The value of FDG PET/CT imaging in outcome prediction and response assessment of lymphoma patients treated with immunotherapy: a meta-analysis and systematic review.

Publisher: Springer Science and Business Media LLC

Date: 06-08-2022

DOI: 10.1007/S00259-022-05918-2

Abstract: Treatment strategies of lymphoid malignancies have been revolutionized by immunotherapy. Because of the inherent property of Hodgkin lymphoma and some subtypes of non-Hodgkin lymphoma as a highly FDG-avid tumor, functional 18 F-FDG PET/CT imaging is already embedded in their routine care. Nevertheless, the question is whether it is still valuable in the context of these tumors being treated with immunotherapy. Herein, we will review the value of 18 F-FDG PET/CT imaging lymphoid tumors treated with immunotherapy regimens. A comprehensive literature search of the PubMed database was conducted on the value of the 18 F-FDG PET/CT for immunotherapy response monitoring of patients with malignant lymphoma. The articles were considered eligible if they met all of the following inclusion criteria: (a) clinical studies on patients with different types of malignant lymphoma, (b) treatment with anti-CD20 antibodies, immune checkpoint inhibitors or immune cell therapies, (c) and incorporated PET/CT with 18 F-FDG as the PET tracer. From the initial 1488 papers identified, 91 were ultimately included in our study. In anti-CD20 therapy, the highest pooled hazard ratios (HRs) of baseline, early, and late response monitoring parameters for progression-free survival (PFS) belong to metabolic tumor volume (MTV) (3.19 (95%CI: 2.36–4.30)), maximum standardized uptake value (SUVmax) (3.25 (95%CI: 2.08–5.08)), and Deauville score (DS) (3.73 (95%CI: 2.50–5.56)), respectively. These measurements for overall survival (OS) were MTV (4.39 (95%CI: 2.71–7.08)), DS (3.23 (95%CI: 1.87–5.58)), and DS (3.64 (95%CI: 1.40–9.43)), respectively. Early and late 18 F-FDG PET/CT response assessment in immune checkpoint inhibitors (ICI) and immune cell therapy might be an effective tool for prediction of clinical outcome. For anti-CD20 therapy of lymphoma, the MTV as a baseline 18 F-FDG PET/CT-derived parameter has the highest HRs for PFS and OS. The DS as visual criteria in early and late response assessment has higher HRs for PFS and OS compared to the international harmonization project (IHP) visual criteria in anti-CD20 therapy. Early changes in 18 F-FDG PET parameters may be predictive of response to ICIs and cell therapy in lymphoma patients.

Pembrolizumab in relapsed or refractory Richter syndrome

Publisher: Wiley

Date: 16-06-2020

DOI: 10.1111/BJH.16762

Improving outcomes for patients with lymphoma: design and development of the Australian and New Zealand Lymphoma and Related Diseases Registry

Publisher: Springer Science and Business Media LLC

Date: 10-10-2022

DOI: 10.1186/S12874-022-01728-0

Abstract: Lymphoma is a malignancy of lymphocytes and lymphoid tissues comprising a heterogeneous group of diseases, with up to 80 entities now described. Lymphoma is the 6 th most common cancer in Australia, affecting patients of all ages, with rising incidence rates. With the proliferation of efficacious novel agents, therapeutic strategies are increasingly erse and survival is improving. There is a clear need for contemporary robust and detailed data on diagnostic, investigational and management strategies for this disease in Australia, New Zealand and worldwide, to inform and benchmark local and international standards of care. Clinical quality registries can provide these data, and support development of strategies to address variations in management, including serving as platforms for clinical trials and other research activities. The Lymphoma and Related Diseases Registry (LaRDR) was developed to capture details of patient demographics, disease characteristics, and management throughout their disease course and therapy and to develop outcome benchmarks nationally and internationally for lymphoma. This report describes the aims, development and implementation of the LaRDR, as well as challenges addressed in the process. The LaRDR was established in 2016 as a multicentre, collaborative project at sites across Australia with a secure online database which collects prospective data on patients with a new diagnosis of lymphoma or chronic lymphocytic leukaemia (CLL). LaRDR development required multidisciplinary participation including specialist haematology, information technology, and biostatistical support, as well as secure funding. Here we describe the database development, data entry, ethics approval process, registry governance and support for participating sites and the coordinating centre. To date more than 5,300 patients have been enrolled from 28 sites in Australia and New Zealand. Multiple challenges arose during the development, which we describe, along with approaches used to overcome them. Several confirmed international collaborations are now in place, and the registry is providing valuable data for clinicians, researchers, industry and government, including through presentations of results at major national and international conferences. Challenges in establishing the LaRDR have been successfully overcome and the registry is now a valuable resource for lymphoma clinicians, researchers, health economists and others in Australia, New Zealand and globally.

Olivia Newton-John Cancer Research And Wellness Centre, Austin Health

Location: Australia

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Eastern Health

Location: Australia

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University Of Melbourne

Location: Australia

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Monash University

Location: Australia

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Biomarker-driven Applications Of Immunotherapy In Lymphoma

Start Date: 2018

End Date: 2021

Funder: National Health and Medical Research Council

Optimising Novel Therapies To Improve Lymphoma Patient Outcomes

Start Date: 2022

End Date: 2021

Funder: National Health and Medical Research Council