Publications by authors named "Tebbutt N"

Background: Panitumumab (pan) plus chemotherapy is a preferred first-line therapy for unresectable RAS and BRAF wild type metastatic colorectal cancer (mCRC). Older patients may not be suitable for combination regimens. We investigated 2 lower intensity pan-containing regimens.

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Introduction: Resection of primary tumor and liver metastases is the gold standard for colorectal cancer with liver-only metastases (CRLM). Although treatment options have expanded to enable conversion of unresectable to resectable CRLM, about 40% of patients will have definitively unresectable disease. Major advances in surgical techniques, immunosuppressive protocols and patient selection criteria for liver transplantation have resulted in improved outcomes.

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  • Regorafenib, an oral multikinase inhibitor, was tested in the INTEGRATE IIa trial to see if it improves overall survival in patients with advanced gastric and esophagogastric junction cancer who did not respond to at least two prior treatments.
  • The trial compared regorafenib plus supportive care against a placebo with supportive care, enrolling 251 participants and evaluating various outcomes like overall survival (OS), progression-free survival (PFS), and quality of life (QoL).
  • Results showed that regorafenib significantly improved OS and PFS compared to placebo, with a median OS of 4.5 months for those receiving regorafenib versus 4.0 months for those on placebo, while also
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The presence of precursor to exhausted (T) CD8 T cells is important to maintain robust immunity following treatment with immune checkpoint inhibition (ICI). Impressive responses to ICI are emerging in patients with stage II-III mismatch repair (MMR)-deficient (dMMR) colorectal cancer (CRC). We found 64% of dMMR and 15% of mismatch repair-proficient (pMMR) stage III CRCs had a high frequency of tumor infiltrating lymphocytes (TIL-hi).

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  • * Results showed that NLM patients generally had better overall survival (OS) and progression-free survival (PFS) than LM patients in first-line and second-line chemotherapy, while OR rates were higher for LM patients overall.
  • * The findings indicate that LM serves as a negative prognostic factor in mCRC, supporting its use in stratifying patients in future clinical trials.
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  • Palliative radiotherapy (RT) and systemic treatments like immunotherapy are increasingly used together for advanced hepatocellular carcinoma (HCC), but there are no established guidelines for their combined use.
  • A review of literature from 2011 to 2023 highlighted 67 studies that examined toxicity after concurrent RT and targeted therapies, including sorafenib, regorafenib, and bevacizumab.
  • Findings showed significant severe liver and gastrointestinal toxicities associated with these combinations, indicating a need for further research to understand their safety and guide treatment decisions for HCC patients.
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Purpose: Open-label phase II study (RELATIVITY-060) to investigate the efficacy and safety of first-line nivolumab, a PD-1-blocking antibody, plus relatlimab, a lymphocyte-activation gene 3 (LAG-3)-blocking antibody, plus chemotherapy in patients with previously untreated advanced gastric cancer (GC) or gastroesophageal junction cancer (GEJC).

Methods: Patients with unresectable, locally advanced or metastatic GC/GEJC were randomly assigned 1:1 to nivolumab + relatlimab (fixed-dose combination) + chemotherapy or nivolumab + chemotherapy. The primary end point was objective response rate (ORR; per RECIST v1.

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Introduction: Although contact days-days with health-care contact outside home-are increasingly adopted as a measure of time toxicity and treatment burden, they could also serve as a surrogate of treatment-related harm. We sought to assess the association between contact days and patient-reported outcomes and the prognostic ability of contact days.

Methods: We conducted a secondary analysis of CO.

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Purpose: Gastric cancers commonly spread to the peritoneum. Its presence significantly alters patient prognosis and treatment-intent; however, current methods of peritoneal staging are inaccurate. Peritoneal tumor DNA (ptDNA) is tumor-derived DNA detectable in peritoneal lavage fluid.

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  • * Research indicates that the effectiveness of this combination is hindered by its inability to induce cell death (apoptosis), despite changes in related proteins, suggesting that MCL-1 and BCL-X are overexpressed in BRAF CRCs.
  • * Combining encorafenib with BCL-X inhibitors has shown promise in enhancing apoptosis in cancer cells, with one experimental approach (DT2216) resulting in increased cell death in lab tests and successful tumor growth reduction
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Predictive drug testing of patient-derived tumor organoids (PDTOs) holds promise for personalizing treatment of metastatic colorectal cancer (mCRC), but prospective data are limited to chemotherapy regimens with conflicting results. We describe a unified framework for PDTO-based predictive testing across standard-of-care chemotherapy and biologic and targeted therapy options. In an Australian community cohort, PDTO predictions based on treatment-naive patients (n = 56) and response rates from first-line mCRC clinical trials achieve 83% accuracy for forecasting responses in patients receiving palliative treatments (18 patients, 29 treatments).

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Background: SCORE is the first randomised controlled trial (RCT) to examine shared oncologist and general practitioner (GP) follow-up for survivors of colorectal cancer (CRC). SCORE aimed to show that shared care (SC) was non-inferior to usual care (UC) on the EORTC QLQ-C30 Global Health Status/Quality of Life (GHQ-QoL) scale to 12 months.

Methods: The study recruited patients from five public hospitals in Melbourne, Australia between February 2017 and May 2021.

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Peritoneal metastases from various abdominal cancer types are common and carry poor prognosis. The presence of peritoneal disease upstages cancer diagnosis and alters disease trajectory and treatment pathway in many cancer types. Therefore, accurate and timely detection of peritoneal disease is crucial.

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Unlabelled: Metastatic colorectal cancer (mCRC) is a heterogeneous disease that can evoke discordant responses to therapy among different lesions in individual patients. The Response Evaluation Criteria in Solid Tumors (RECIST) criteria do not take into consideration response heterogeneity. We explored and developed lesion-based measurement response criteria to evaluate their prognostic effect on overall survival (OS).

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Aims: The Symptom and Urgent Review Clinic was a service improvement initiative, which consisted of the implementation and evaluation of a nurse-led emergency department (ED) avoidance model of care. The clinic was developed for patients experiencing symptoms associated with systemic anti-cancer therapy in ambulatory cancer settings.

Methods: The clinic was implemented in four health services in Melbourne, Australia across a six-month period in 2018.

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Background: The Victorian Government convened the second Pancreas Cancer Summit in 2021 to identify unwarranted variation in care 2016-2019, and to assess trends compared with the first Summit 2017 (reporting 2011-2015). State-wide administrative data were assessed at population level in alignment with optimal care pathways across all stages of the cancer care continuum.

Methods: Data linkage performed by Centre for Victorian Data Linkage combined data from Victorian Cancer Registry with other administrative data sets including Victorian Admitted Episodes Dataset, Victorian Radiotherapy Minimum Data Set, Victorian Emergency Minimum Dataset and Victorian Death Index.

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Purpose: The time spent in pursuing treatments for advanced cancer can be substantial. We have previously proposed a pragmatic and patient-centered metric of these time costs-which we term time toxicity-as any day with physical health care system contact. This includes outpatient visits (eg, bloodwork, scans, etc), emergency department visits, and overnight stays in a health care facility.

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Background: Advanced gastro-oesophageal cancer (AGOC) carries a poor prognosis. No standard of care treatment options are available after first and second-line therapies. Regorafenib is an oral multi-targeted tyrosine kinase inhibitor targeting angiogenic, stromal, and oncogenic receptor tyrosine kinases.

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Adherens junctions (AJs) are a defining feature of all epithelial cells. They regulate epithelial tissue architecture and integrity, and their dysregulation is a key step in tumor metastasis. AJ remodeling is crucial for cancer progression, and it plays a key role in tumor cell survival, growth, and dissemination.

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Purpose: BRAF V600E mutant metastatic colorectal cancer represents a significant clinical problem, with combination approaches being developed clinically with oral BRAF inhibitors combined with EGFR-targeting antibodies. While compelling preclinical data have highlighted the effectiveness of combination therapy with vemurafenib and small-molecule EGFR inhibitors, gefitinib or erlotinib, in colorectal cancer, this therapeutic strategy has not been investigated in clinical studies.

Patients And Methods: We conducted a phase Ib/II dose-escalation/expansion trial investigating the safety/efficacy of the BRAF inhibitor vemurafenib and EGFR inhibitor erlotinib.

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Purpose: Napabucasin is an investigational, orally administered reactive oxygen species generator bioactivated by intracellular antioxidant NAD(P)H:quinone oxidoreductase 1 that has been evaluated in various solid tumors, including metastatic colorectal cancer (mCRC). Phosphorylated signal transducer and activator of transcription 3 (pSTAT3) is hypothesized to predict response in napabucasin-treated patients with mCRC.

Patient And Methods: In the multi-center, open-label, phase III CanStem303C (NCT02753127) study, adults with histologically confirmed mCRC that progressed on first-line fluoropyrimidine plus oxaliplatin ± bevacizumab were randomized to twice-daily napabucasin plus FOLFIRI (napabucasin) or FOLFIRI alone (control).

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