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  1. Article ; Online: Peritoneal Tumor DNA as a Prognostic Biomarker in Gastric Cancer: A Systematic Review and Meta-Analysis.

    Allan, Zexi / Witts, Sasha / Wong, Darren J / Lee, Margaret M / Tie, Jeanne / Tebbutt, Niall C / Clemons, Nicholas J / Liu, David S

    JCO precision oncology

    2024  Volume 8, Page(s) e2300546

    Abstract: 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 ... ...

    Abstract 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. ptDNA positivity may indicate peritoneal micrometastasis and may be more sensitive than cytology in staging the peritoneum. In this meta-analysis, we evaluated the prognostic potential of ptDNA in gastric cancer.
    Methods: PubMed, Embase, Scopus, and Web of Science databases were searched using PRISMA guidelines. Studies published between January 1, 1990, and April 30, 2023, containing quantitative data relating to ptDNA in gastric cancer were meta-analyzed.
    Results: Six studies were analyzed. Of the total 757 patients with gastric adenocarcinoma, 318 (42.0%) were stage I, 311 (41.0%) were stage II/III, 116 (15.3%) were stage IV, and 22 (2.9%) were undetermined. Overall, ptDNA detected cytology-positive cases with a sensitivity and specificity of 85.2% (95% CI, 66.5 to 100.0) and 91.5% (95% CI, 86.5 to 96.6), respectively. Additionally, ptDNA was detected in 54 (8.5%) of 634 cytology-negative patients. The presence of ptDNA negatively correlated with pathological stage I (relative risk [RR], 0.29 [95% CI, 0.13 to 0.66]) and positively correlated with pathological stage IV (RR, 8.61 [95% CI, 1.86 to 39.89]) disease. Importantly, ptDNA positivity predicted an increased risk of peritoneal-specific metastasis (RR, 13.81 [95% CI, 8.11 to 23.53]) and reduced 3-year progression-free (RR, 5.37 [95% CI, 1.39 to 20.74]) and overall (hazard ratio, 4.13 [95% CI, 1.51 to 11.32]) survival.
    Conclusion: ptDNA carries valuable prognostic information and can detect peritoneal micrometastases in patients with gastric cancer. Its clinical utility in peritoneal staging for gastric cancer deserves further investigation.
    MeSH term(s) Humans ; Peritoneum ; Peritoneal Neoplasms/diagnosis ; Peritoneal Neoplasms/genetics ; Prognosis ; Stomach Neoplasms/diagnosis ; Stomach Neoplasms/genetics ; Neoplasm Staging ; DNA ; Biomarkers
    Chemical Substances DNA (9007-49-2) ; Biomarkers
    Language English
    Publishing date 2024-03-21
    Publishing country United States
    Document type Meta-Analysis ; Systematic Review ; Journal Article ; Review
    ISSN 2473-4284
    ISSN (online) 2473-4284
    DOI 10.1200/PO.23.00546
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  2. Article ; Online: Changing patterns of care for pancreas cancer in Victoria: the 2022 Pancreas Tumour Summit.

    Pilgrim, Charles H C / Finn, Norah / Stuart, Ella / Philip, Jennifer / Steel, Simone / Croagh, Dan / Lee, Belinda / Tebbutt, Niall C

    ANZ journal of surgery

    2023  Volume 93, Issue 11, Page(s) 2638–2647

    Abstract: 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 ... ...

    Abstract 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. A Cancer Service Performance Indicator audit was carried out providing an in-depth analysis of identified areas of interest.
    Results: Of 3138 Victorians diagnosed with pancreas ductal adenocarcinoma 2016-2019, 63% were metastatic at diagnosis. One-year survival increased between time periods, from 29.7% overall 2011-2015 (59.1% for non-metastatic, and 15.1% metastatic) to 32.5% overall 2016-2019 (P < 0.001), 61.2% non-metastatic (P = 0.008), 15.7% metastatic (P = NS). A higher proportion of non-metastatic patients progressed to surgery (35% vs. 31%, P = 0.020), and more received neoadjuvant therapy (16% vs. 4%, P < 0.001). Postoperative mortality following pancreatectomy at 30 and 90 days remained low at 2%. Utilization of 5FU-based chemotherapy regimens increased between 2016 and 2020. Multidisciplinary Meeting (MDM) presentation was still below the 85% target (74%) as was supportive care screening (39%, target 80%).
    Conclusions: Surgical outcomes remain world-class and there has been an appropriate shift in chemotherapy administration towards neoadjuvant timing with increasing use of 5FU-based regimens. MDM presentation rates, supportive care and overall care coordination remain areas of deficiency.
    MeSH term(s) Humans ; Hospitalization ; Pancreatic Neoplasms/epidemiology ; Pancreatic Neoplasms/therapy ; Fluorouracil ; Pancreatic Neoplasms
    Chemical Substances Fluorouracil (U3P01618RT)
    Language English
    Publishing date 2023-05-23
    Publishing country Australia
    Document type Journal Article
    ZDB-ID 2050749-5
    ISSN 1445-2197 ; 1445-1433 ; 0004-8682
    ISSN (online) 1445-2197
    ISSN 1445-1433 ; 0004-8682
    DOI 10.1111/ans.18522
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  3. Article ; Online: The association of healthcare contact days with physical function and survival in CCTG/AGITG CO.17.

    Gupta, Arjun / O'Callaghan, Christopher J / Zhu, Liting / Jonker, Derek J / Wong, Ralph P W / Colwell, Bruce / Moore, Malcolm J / Karapetis, Christos S / Tebbutt, Niall C / Shapiro, Jeremy D / Tu, Dongsheng / Booth, Christopher M

    Journal of the National Cancer Institute

    2024  

    Abstract: Introduction: While contact days-days with healthcare 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 ... ...

    Abstract Introduction: While contact days-days with healthcare 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.17 that evaluated cetuximab vs supportive care in patients with advanced colorectal cancer. CO.17 collected EORTC-QLQ-C30 instrument data. We assessed the association between number of contact days in a window and changes in physical function and global health status, and the association between number of contact days in the first 4 weeks with overall survival (OS).
    Results: There was a negative association between the number of contact days and change in physical function (per each additional contact day at 4 weeks, 1.50 point decrease; and 8 weeks, 1.06 point decrease, p < .0001 for both), but not with global health status. This negative association was seen in patients receiving cetuximab, but not supportive care. More contact days in the first 4 weeks was associated with worse OS for all comers and patients receiving cetuximab (per each additional contact day; all comers, aHR 1.07, 95% CI, 1.05- 1.10; and cetuximab, aHR 1.08, 95%CI 1.05- 1.11, p < .0001 for both).
    Conclusions: In this secondary analysis of a clinical trial, more contact days early in the course was associated with declines in physical function and worse survival in all-comers and in participants receiving cancer-directed treatment.
    Trial registration: ClinicalTrials.gov number, NCT00079066.
    Language English
    Publishing date 2024-04-24
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2992-0
    ISSN 1460-2105 ; 0027-8874 ; 0198-0157
    ISSN (online) 1460-2105
    ISSN 0027-8874 ; 0198-0157
    DOI 10.1093/jnci/djae077
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  4. Article ; Online: Evaluating the Time Toxicity of Cancer Treatment in the CCTG CO.17 Trial.

    Gupta, Arjun / O'Callaghan, Christopher J / Zhu, Liting / Jonker, Derek J / Wong, Ralph P W / Colwell, Bruce / Moore, Malcolm J / Karapetis, Christos S / Tebbutt, Niall C / Shapiro, Jeremy D / Tu, Dongsheng / Booth, Christopher M

    JCO oncology practice

    2023  Volume 19, Issue 6, Page(s) e859–e866

    Abstract: 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 ... ...

    Abstract 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. Herein, we sought to assess time toxicity in a completed randomized controlled trial (RCT).
    Methods: We conducted a secondary analysis of the Canadian Cancer Trials Group CO.17 RCT that evaluated weekly cetuximab infusions versus supportive care alone in 572 patients with advanced colorectal cancer. Initial results reported a 6-week improvement in median overall survival (OS) with cetuximab (6.1
    Results: In the overall population, median time toxic days were higher in the cetuximab arm (28
    Conclusion: This proof-of-concept feasibility study demonstrates that measures of time toxicity can be extracted through secondary analyses of RCTs. In CO.17, despite an overall OS benefit with cetuximab, home days were statistically similar across arms. Such data can supplement traditional survival end points in RCTs. Further work should refine and validate the measure prospectively.[Media: see text].
    MeSH term(s) Humans ; Cetuximab ; Antibodies, Monoclonal, Humanized ; Canada ; Colorectal Neoplasms
    Chemical Substances Cetuximab (PQX0D8J21J) ; Antibodies, Monoclonal, Humanized
    Language English
    Publishing date 2023-03-07
    Publishing country United States
    Document type Randomized Controlled Trial ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3028198-2
    ISSN 2688-1535 ; 2688-1527
    ISSN (online) 2688-1535
    ISSN 2688-1527
    DOI 10.1200/OP.22.00737
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  5. Article ; Online: Is there a role for combined anti-PD-1/CTLA-4 checkpoint blockade in the management of advanced biliary tract cancers?

    Klein, Oliver / Kee, Damien / Nagrial, Adnan / Markman, Ben / Underhill, Craig / Michael, Michael / Behren, Andreas / Palmer, Jodie / Tebbutt, Niall C / Carlino, Matteo S / Cebon, Jonathan

    Cancer

    2023  Volume 129, Issue 7, Page(s) 1129–1130

    MeSH term(s) Humans ; CTLA-4 Antigen ; Antibodies, Monoclonal/therapeutic use ; Melanoma ; Bile Duct Neoplasms ; Immunotherapy
    Chemical Substances CTLA-4 Antigen ; Antibodies, Monoclonal
    Language English
    Publishing date 2023-01-24
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 1429-1
    ISSN 1097-0142 ; 0008-543X ; 1934-662X
    ISSN (online) 1097-0142
    ISSN 0008-543X ; 1934-662X
    DOI 10.1002/cncr.34660
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  6. Article: Comparing survival outcomes for patients with colorectal cancer treated in public and private hospitals.

    Tebbutt, Niall C

    The Medical journal of Australia

    2007  Volume 187, Issue 4, Page(s) 250; author reply 251

    MeSH term(s) Colorectal Neoplasms/mortality ; Colorectal Neoplasms/pathology ; Colorectal Neoplasms/therapy ; Hospitals, Private ; Hospitals, Public ; Humans ; Treatment Outcome
    Language English
    Publishing date 2007-07-31
    Publishing country Australia
    Document type Comment ; Journal Article
    ZDB-ID 186082-3
    ISSN 1326-5377 ; 0025-729X
    ISSN (online) 1326-5377
    ISSN 0025-729X
    DOI 10.5694/j.1326-5377.2007.tb01219.x
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  7. Article ; Online: Personalizing First-Line Systemic Therapy in Metastatic Colorectal Cancer: Is There a Role for Initial Low-Intensity Therapy in 2021 and Beyond? A Perspective From Members of the Australasian Gastrointestinal Trials Group.

    Dunn, Catherine / Hong, Wei / Gibbs, Peter / Ackland, Stephen / Sjoquist, Katrin / Tebbutt, Niall C / Price, Timothy / Burge, Matthew

    Clinical colorectal cancer

    2021  Volume 20, Issue 3, Page(s) 245–255

    Abstract: Palliative chemotherapy is the cornerstone of treatment for the majority of patients with metastatic colorectal cancer, with the aim of increasing length and quality of life. Although guidelines outline the available treatment options in the first line, ... ...

    Abstract Palliative chemotherapy is the cornerstone of treatment for the majority of patients with metastatic colorectal cancer, with the aim of increasing length and quality of life. Although guidelines outline the available treatment options in the first line, they provide limited guidance on choice and intensity of the chemotherapy backbone. Data from the TRIBE and TRIBE2 studies confirm a survival benefit with triplet FOLFOXIRI and bevacizumab, and this is a preferred option for younger patients with good performance status able to tolerate it. However, the relative benefit of a fluoropyrimidine doublet with oxaliplatin or irinotecan over single-agent fluoropyrimidine with or without a biologic is less certain; the available data demonstrate that single-agent fluoropyrimidine plus a biologic with planned sequencing of subsequent agents can produce similar overall survival outcomes with reduced toxicity. Our analysis of local real-world registry data suggests that this is an underutilized approach, particularly in younger and fitter patients. Established prognostic factors, including patient age, performance status, tumor sidedness, and biomarkers such as RAS/BRAF, are key in treatment selection; patients with left-sided RAS/BRAF wild-type disease or patients with low tumor bulk may be ideal for a less intensive regimen. Further studies are required to confirm the value of less-intensive regimens in the modern era, where the incorporation of biologic therapies has become routine and where non-chemotherapy options are emerging as viable options for molecularly defined patient subsets.
    MeSH term(s) Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Bevacizumab/therapeutic use ; Colorectal Neoplasms/drug therapy ; Fluorouracil/therapeutic use ; Humans ; Leucovorin/therapeutic use ; Quality of Life
    Chemical Substances Bevacizumab (2S9ZZM9Q9V) ; Leucovorin (Q573I9DVLP) ; Fluorouracil (U3P01618RT)
    Language English
    Publishing date 2021-05-11
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2112638-0
    ISSN 1938-0674 ; 1533-0028
    ISSN (online) 1938-0674
    ISSN 1533-0028
    DOI 10.1016/j.clcc.2021.05.001
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    Zs.A 5798: Show issues Location:
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    Zs.MO 435: Show issues

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  8. Article ; Online: BCL-X

    Jenkins, Laura J / Luk, Ian Y / Chionh, Fiona / Tan, Tao / Needham, Kristen / Ayton, Jamieson / Reehorst, Camilla M / Vukelic, Natalia / Sieber, Oliver M / Mouradov, Dmitri / Gibbs, Peter / Williams, David S / Tebbutt, Niall C / Desai, Jayesh / Hollande, Frédéric / Dhillon, Amardeep S / Lee, Erinna F / Merino, Delphine / Fairlie, W Douglas /
    Mariadason, John M

    Cell death & disease

    2024  Volume 15, Issue 3, Page(s) 183

    Abstract: Metastatic ... ...

    Abstract Metastatic BRAF
    MeSH term(s) Animals ; Humans ; Mice ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; bcl-X Protein/antagonists & inhibitors ; bcl-X Protein/metabolism ; Carbamates ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/genetics ; Myeloid Cell Leukemia Sequence 1 Protein/genetics ; Myeloid Cell Leukemia Sequence 1 Protein/metabolism ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Proto-Oncogene Proteins B-raf/antagonists & inhibitors ; Proto-Oncogene Proteins B-raf/genetics ; Sulfonamides/pharmacology ; Sulfonamides/therapeutic use ; Apoptosis/drug effects
    Chemical Substances Antineoplastic Agents ; bcl-X Protein ; BRAF protein, human (EC 2.7.11.1) ; Carbamates ; encorafenib (8L7891MRB6) ; Myeloid Cell Leukemia Sequence 1 Protein ; Protein Kinase Inhibitors ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; Sulfonamides ; DT2216
    Language English
    Publishing date 2024-03-01
    Publishing country England
    Document type Journal Article
    ZDB-ID 2541626-1
    ISSN 2041-4889 ; 2041-4889
    ISSN (online) 2041-4889
    ISSN 2041-4889
    DOI 10.1038/s41419-024-06478-z
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  9. Article ; Online: Bevacizumab in colorectal cancer: current and future directions.

    Yeung, Yvonne / Tebbutt, Niall C

    Expert review of anticancer therapy

    2012  Volume 12, Issue 10, Page(s) 1263–1273

    Abstract: Bevacizumab is a humanized monoclonal antibody to VEGF-A, an important therapeutic target through its proangiogenic effects on a variety of tumors. Bevacizumab has demonstrated clinically meaningful benefit in conjunction with chemotherapy for patients ... ...

    Abstract Bevacizumab is a humanized monoclonal antibody to VEGF-A, an important therapeutic target through its proangiogenic effects on a variety of tumors. Bevacizumab has demonstrated clinically meaningful benefit in conjunction with chemotherapy for patients with metastatic colorectal cancer as well as other tumor types. Bevacizumab is a well-tolerated therapy with regard to toxicity, in keeping with its biological vascular effect. In this era of personalized medicine, current Phase II and III trials are further defining its role at various stages of metastatic disease and the optimal sequencing with cytotoxic and other targeted agents to achieve further improvements in patient outcome. Translational research for biomarker discovery and validation and further study into mechanisms of resistance are essential for future development and sustained benefit with this class of therapeutic agents.
    MeSH term(s) Angiogenesis Inhibitors/adverse effects ; Angiogenesis Inhibitors/pharmacokinetics ; Angiogenesis Inhibitors/pharmacology ; Angiogenesis Inhibitors/therapeutic use ; Animals ; Antibodies, Monoclonal, Humanized/adverse effects ; Antibodies, Monoclonal, Humanized/pharmacokinetics ; Antibodies, Monoclonal, Humanized/pharmacology ; Antibodies, Monoclonal, Humanized/therapeutic use ; Bevacizumab ; Biomarkers, Tumor/metabolism ; Clinical Trials as Topic ; Colorectal Neoplasms/blood supply ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/metabolism ; Drug Resistance, Neoplasm ; Humans ; Randomized Controlled Trials as Topic
    Chemical Substances Angiogenesis Inhibitors ; Antibodies, Monoclonal, Humanized ; Biomarkers, Tumor ; Bevacizumab (2S9ZZM9Q9V)
    Language English
    Publishing date 2012-10
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2112544-2
    ISSN 1744-8328 ; 1473-7140
    ISSN (online) 1744-8328
    ISSN 1473-7140
    DOI 10.1586/era.12.104
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  10. Article ; Online: Author Correction: DUSP5 is methylated in CIMP-high colorectal cancer but is not a major regulator of intestinal cell proliferation and tumorigenesis.

    Tögel, Lars / Nightingale, Rebecca / Wu, Rui / Chüeh, Anderly C / Al-Obaidi, Sheren / Luk, Ian / Dávalos-Salas, Mercedes / Chionh, Fiona / Murone, Carmel / Buchanan, Daniel D / Chatterton, Zac / Sieber, Oliver M / Arango, Diego / Tebbutt, Niall C / Williams, David / Dhillon, Amardeep S / Mariadason, John M

    Scientific reports

    2023  Volume 13, Issue 1, Page(s) 2422

    Language English
    Publishing date 2023-02-10
    Publishing country England
    Document type Published Erratum
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-023-29328-y
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