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Article ; Online: Integrating Functional Imaging and Molecular Profiling for Optimal Treatment Selection in Neuroendocrine Neoplasms (NEN).

Kong, Grace / Boehm, Emma / Prall, Owen / Murray, William K / Tothill, Richard W / Michael, Michael

2023 Volume 25, Issue 5, Page(s) 465–478

Abstract: Purpose of review: Gastroenteropancreatic NEN (GEP-NEN) are group of malignancies with significant clinical, anatomical and molecular heterogeneity. High-grade GEP-NEN in particular present unique management challenges.: Recent findings: In the ... ...

Abstract	Purpose of review: Gastroenteropancreatic NEN (GEP-NEN) are group of malignancies with significant clinical, anatomical and molecular heterogeneity. High-grade GEP-NEN in particular present unique management challenges. Recent findings: In the current era, multidisciplinary management with access to a combination of functional imaging and targeted molecular profiling can provide important disease characterisation, guide individualised management and improve patient outcome. Multiple treatment options are now available, and combination and novel therapies are being explored in clinical trials. Precision medicine is highly relevant for a heterogenous disease like NEN. The integration of dual-tracer functional PET/CT imaging, molecular histopathology and genomic data has the potential to be used to gain a more comprehensive understanding of an individual patient's disease biology for precision diagnosis, prognostication and optimal treatment allocation.
MeSH term(s)	Humans ; Positron Emission Tomography Computed Tomography ; Gastrointestinal Neoplasms/diagnostic imaging ; Gastrointestinal Neoplasms/genetics ; Gastrointestinal Neoplasms/therapy ; Neuroendocrine Tumors/diagnostic imaging ; Neuroendocrine Tumors/genetics ; Neuroendocrine Tumors/therapy ; Pancreatic Neoplasms/diagnostic imaging ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/therapy ; Intestinal Neoplasms/diagnostic imaging ; Intestinal Neoplasms/genetics ; Intestinal Neoplasms/therapy ; Stomach Neoplasms/diagnostic imaging ; Stomach Neoplasms/genetics ; Stomach Neoplasms/therapy
Language	English
Publishing date	2023-02-24
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2057359-5
ISSN	1534-6269 ; 1523-3790
ISSN (online)	1534-6269
ISSN	1523-3790
DOI	10.1007/s11912-023-01381-w
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Zs.A 5521: Show issues

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Article ; Online: A genome-wide CRISPR/Cas9 screen identifies DNA-PK as a sensitiser to

Waldeck, Kelly / Van Zuylekom, Jessica / Cullinane, Carleen / Gulati, Twishi / Simpson, Kaylene J / Tothill, Richard W / Blyth, Benjamin / Hicks, Rodney J

Theranostics

2023 Volume 13, Issue 14, Page(s) 4745–4761

Abstract: Peptide receptor radionuclide therapy (PRRT) ... ...

Abstract	Peptide receptor radionuclide therapy (PRRT) using
MeSH term(s)	Animals ; Humans ; Mice ; CRISPR-Cas Systems/genetics ; DNA ; Lutetium/metabolism ; Neuroendocrine Tumors/genetics ; Neuroendocrine Tumors/radiotherapy ; Octreotide/therapeutic use ; Radioisotopes/therapeutic use
Chemical Substances	1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid (1HTE449DGZ) ; DNA (9007-49-2) ; Lutetium (5H0DOZ21UJ) ; Octreotide (RWM8CCW8GP) ; Radioisotopes
Language	English
Publishing date	2023-08-28
Publishing country	Australia
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2592097-2
ISSN	1838-7640 ; 1838-7640
ISSN (online)	1838-7640
ISSN	1838-7640
DOI	10.7150/thno.84628
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Article ; Online: A qualitative study of patients with Cancer of Unknown Primary: Perceptions of communication, understanding of diagnosis and genomic testing, and information needs.

Wolyniec, Kamil / O'Callaghan, Clare / Fisher, Krista / Jessica, Sharp / Tothill, Richard W / Bowtell, David / Linda, Mileshkin / Schofield, Penelope

Psycho-oncology

2023 Volume 32, Issue 4, Page(s) 589–596

Abstract: Objective: Patients with Cancer of Unknown Primary (CUP) commonly report poor understanding of their illness and high levels of psychological distress. Despite the potential benefits to CUP patients, there is a paucity of research exploring the reasons ... ...

Abstract	Objective: Patients with Cancer of Unknown Primary (CUP) commonly report poor understanding of their illness and high levels of psychological distress. Despite the potential benefits to CUP patients, there is a paucity of research exploring the reasons behind poor understanding of a CUP diagnosis. The aim of this study was to understand patients' experiences of communication with doctors, their understanding of diagnosis and the role of genomic testing, as well as their information needs. Methods: Semi-structured interviews explored CUP patients' perceptions of communication with their doctors, understanding of their illness, and their needs regarding medical information. Qualitative inductive thematic analysis of transcribed audio-recordings was employed. Setting/participants: Nineteen patients were recruited from within a prospective cohort study involving routine genomic testing of CUP patients. Results: CUP patients had varied perceptions of communication with doctors as well as different levels of need, readiness, and capacity for information. Some patients felt well understood and supported by their doctors while others did not. Many patients reported feeling overwhelmed and shocked when receiving their cancer diagnosis and emphasized the importance of family support in receiving and understanding medical information. While patients understood the implications of genomic testing for treatment and diagnosis, few had a detailed understanding of genomic testing. Conclusions: Patients' experience of communication and understanding of CUP could be potentially improved by clinicians' assessment of the communication style preferred by each patient and their family and the development of online resources to meet their evolving information needs.
MeSH term(s)	Humans ; Neoplasms, Unknown Primary/diagnosis ; Prospective Studies ; Communication ; Physicians/psychology ; Genetic Testing ; Qualitative Research
Language	English
Publishing date	2023-02-13
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1118536-3
ISSN	1099-1611 ; 1057-9249
ISSN (online)	1099-1611
ISSN	1057-9249
DOI	10.1002/pon.6104
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Zs.A 3550: Show issues

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Article ; Online: Psychological distress, understanding of cancer and illness uncertainty in patients with Cancer of Unknown Primary.

Wolyniec, Kamil / Sharp, Jessica / Fisher, Krista / Tothill, Richard W / Bowtell, David / Mileshkin, Linda / Schofield, Penelope

Psycho-oncology

2022 Volume 31, Issue 11, Page(s) 1869–1876

Abstract: Objective: Patients diagnosed with Cancer of Unknown Primary (CUP) experience high levels of psychological distress and report poor understanding of their cancer. We aimed to investigate: (1) if CUP patients with poorer understanding of their cancer ... ...

Abstract	Objective: Patients diagnosed with Cancer of Unknown Primary (CUP) experience high levels of psychological distress and report poor understanding of their cancer. We aimed to investigate: (1) if CUP patients with poorer understanding of their cancer diagnosis and testing experience more symptoms of psychological distress than those with better understanding; (2) if the relationship between patients' understanding of their cancer and psychological distress is mediated by illness uncertainty; and (3) explore whether patients' degree of understanding of their cancer can be predicted by clinical and socio-demographic factors. Methods: 209 CUP patients completed a questionnaire measuring anxiety, depression, illness uncertainty, fatigue, pain, sleep and understanding of their cancer. Using an apriori theoretical framework, we employed structural equation modelling to investigate predictors of patient's understanding of their cancer and psychological distress and the relationships between understanding, illness uncertainty and distress. Results: The structural equation model displayed good fit indices and supported the hypothesised relationship of patient's understanding of their cancer and the extent of psychological distress, which was mediated via illness uncertainty. Physical symptoms were positively associated with psychological distress and illness uncertainty. Younger age was predictive of lower patient's understanding of their cancer and higher levels of psychological distress. Conclusions: Patients with CUP, particularly those who are younger and experiencing more physical symptoms, report higher levels of psychological distress and may require additional mental health support. Our findings highlight a need to improve CUP patient's understanding about their illness, which could help reduce their illness uncertainty and alleviate psychological distress.
MeSH term(s)	Humans ; Uncertainty ; Neoplasms, Unknown Primary ; Psychological Distress ; Anxiety/epidemiology ; Anxiety/psychology ; Fatigue/epidemiology ; Stress, Psychological/psychology ; Depression/epidemiology ; Depression/psychology
Language	English
Publishing date	2022-07-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1118536-3
ISSN	1099-1611 ; 1057-9249
ISSN (online)	1099-1611
ISSN	1057-9249
DOI	10.1002/pon.5990
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Article ; Online: FAPI PET/CT: Will It End the Hegemony of

Hicks, Rodney J / Roselt, Peter J / Kallur, Kumarswamy G / Tothill, Richard W / Mileshkin, Linda

Journal of nuclear medicine : official publication, Society of Nuclear Medicine

2020 Volume 62, Issue 3, Page(s) 296–302

Abstract: For over 40 years, ...

Abstract	For over 40 years,
MeSH term(s)	Blood Proteins/metabolism ; Fluorodeoxyglucose F18 ; Humans ; Neoplasms/diagnostic imaging ; Neoplasms/metabolism ; Positron Emission Tomography Computed Tomography
Chemical Substances	Blood Proteins ; fibroblast chemotactic inhibitor ; Fluorodeoxyglucose F18 (0Z5B2CJX4D)
Language	English
Publishing date	2020-12-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	80272-4
ISSN	1535-5667 ; 0097-9058 ; 0161-5505 ; 0022-3123
ISSN (online)	1535-5667
ISSN	0097-9058 ; 0161-5505 ; 0022-3123
DOI	10.2967/jnumed.120.256271
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Zs.A 114: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Six-year experience of Australia's first dedicated cancer of unknown primary clinic.

van Mourik, Arielle / Tonkin-Hill, Gina / O'Farrell, John / Waller, Shohei / Tan, Lavinia / Tothill, Richard W / Bowtell, David / Fox, Stephen / Fellowes, Andrew / Fedele, Clare / Schofield, Penelope / Sivakumaran, Tharani / Wong, Hui-Li / Mileshkin, Linda

British journal of cancer

2023 Volume 129, Issue 2, Page(s) 301–308

Abstract: Background: Diagnosis and management of cancers of unknown primary (CUP) remain challenging. This study examines the referral patterns, management and outcomes of patients referred to Australia's first dedicated CUP clinic.: Methods: Retrospective ... ...

Abstract	Background: Diagnosis and management of cancers of unknown primary (CUP) remain challenging. This study examines the referral patterns, management and outcomes of patients referred to Australia's first dedicated CUP clinic. Methods: Retrospective medical record review was conducted for patients seen at the Peter MacCallum Cancer Centre CUP clinic between July 2014 and August 2020. Overall survival (OS) was analysed for patients with a CUP diagnosis where treatment information was available. Results: Of 361 patients referred, fewer than half had completed diagnostic work-up at the time of referral. A diagnosis of CUP was established in 137 (38%), malignancy other than CUP in 177 (49%) and benign pathology in 36 (10%) patients. Genomic testing was successfully completed in 62% of patients with initial provisional CUP and impacted management in 32% by identifying a tissue of origin or actionable genomic alteration. The use of site-specific, targeted therapy or immunotherapy was independently associated with longer OS compared to empirical chemotherapy. Conclusion: Our specialised CUP clinic facilitated diagnostic work-up among patients with suspected malignancy and provided access to genomic testing and clinical trials for patients with a CUP diagnosis, all of which are important to improve outcomes in this patient population.
MeSH term(s)	Humans ; Neoplasms, Unknown Primary/diagnosis ; Neoplasms, Unknown Primary/genetics ; Neoplasms, Unknown Primary/therapy ; Retrospective Studies ; Genomics ; Gene Expression Profiling ; Australia/epidemiology
Language	English
Publishing date	2023-05-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80075-2
ISSN	1532-1827 ; 0007-0920
ISSN (online)	1532-1827
ISSN	0007-0920
DOI	10.1038/s41416-023-02254-6
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Uh III Zs.142: Show issues

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Article ; Online: Wet or Dry? Do Liquid Biopsy Techniques Compete with or Complement PET for Disease Monitoring in Oncology?

Wong, Stephen Q / Tothill, Richard W / Dawson, Sarah-Jane / Hicks, Rodney J

Journal of nuclear medicine : official publication, Society of Nuclear Medicine

2017 Volume 58, Issue 6, Page(s) 869–870

MeSH term(s)	Biomarkers, Tumor/analysis ; DNA, Neoplasm/analysis ; Humans ; Liquid Biopsy ; Medical Oncology/methods ; Monitoring, Physiologic ; Neoplasms/diagnostic imaging ; Neoplasms/therapy ; Positron-Emission Tomography
Chemical Substances	Biomarkers, Tumor ; DNA, Neoplasm
Language	English
Publishing date	2017-04-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	80272-4
ISSN	1535-5667 ; 0097-9058 ; 0161-5505 ; 0022-3123
ISSN (online)	1535-5667
ISSN	0097-9058 ; 0161-5505 ; 0022-3123
DOI	10.2967/jnumed.117.190116
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Zs.A 114: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Rapid Point-of-Care Electrochemical Sensor for the Detection of Cancer Tn Antigen Carbohydrate in Whole Unprocessed Blood.

M Silva, Saimon / Langley, Daniel P / Cossins, Luke R / Samudra, Anushka N / Quigley, Anita F / Kapsa, Robert M I / Tothill, Richard W / Greene, George W / Moulton, Simon E

ACS sensors

2022 Volume 7, Issue 11, Page(s) 3379–3388

Abstract: Improving outcomes for cancer patients during treatment and monitoring for cancer recurrence requires personalized care which can only be achieved through regular surveillance for biomarkers. Unfortunately, routine detection for blood-based biomarkers is ...

Abstract	Improving outcomes for cancer patients during treatment and monitoring for cancer recurrence requires personalized care which can only be achieved through regular surveillance for biomarkers. Unfortunately, routine detection for blood-based biomarkers is cost-prohibitive using currently specialized laboratories. Using a rapid self-assembly sensing interface amenable to methods of mass production, we demonstrate the ability to detect and quantify a small carbohydrate-based cancer biomarker, Tn antigen (αGalNAc-Ser/Thr) in a small volume of blood, using a test format strip reminiscent of a blood glucose test. The detection of Tn antigen at picomolar levels is achieved through a new transduction mechanism based on the impact of Tn antigen interactions on the molecular dynamic motion of a lectin cross-linked lubricin antifouling brush. In tests performed on retrospective blood plasma samples from patients presenting three different tumor types, differentiation between healthy and diseased patients was achieved, highlighting the clinical potential for cancer monitoring.
MeSH term(s)	Humans ; Point-of-Care Systems ; Retrospective Studies ; Neoplasms/diagnosis ; Carbohydrates
Chemical Substances	Tn antigen ; Carbohydrates
Language	English
Publishing date	2022-11-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2379-3694
ISSN (online)	2379-3694
DOI	10.1021/acssensors.2c01460
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Article ; Online: Enhancing the anti-tumour activity of

Cullinane, Carleen / Waldeck, Kelly / Kirby, Laura / Rogers, Buck E / Eu, Peter / Tothill, Richard W / Hicks, Rodney J

Scientific reports

2020 Volume 10, Issue 1, Page(s) 10196

Abstract: Peptide receptor radionuclide therapy (PRRT) is an important treatment option for patients with somatostatin receptor-2 (SSTR2)-expressing neuroendocrine tumour (NET) though tumour regression occurs in only a minority of patients. Therefore, novel PRRT ... ...

Abstract	Peptide receptor radionuclide therapy (PRRT) is an important treatment option for patients with somatostatin receptor-2 (SSTR2)-expressing neuroendocrine tumour (NET) though tumour regression occurs in only a minority of patients. Therefore, novel PRRT regimens with improved therapeutic activity are needed. Radiation induced DNA damage repair is an attractive therapeutic target to increase PRRT efficacy and consequently, we have characterised a panel of preclinical models for their SSTR2 expression, in vivo growth properties and response to
MeSH term(s)	Animals ; Antineoplastic Agents/pharmacology ; Cell Line, Tumor ; Humans ; Lutetium/physiology ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neuroendocrine Tumors/drug therapy ; Octreotide/analogs & derivatives ; Octreotide/pharmacology ; Organometallic Compounds/pharmacology ; Phthalazines/pharmacology ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology ; Poly(ADP-ribose) Polymerases/metabolism ; Radioisotopes ; Radiopharmaceuticals/pharmacology ; Receptors, Somatostatin/metabolism
Chemical Substances	Antineoplastic Agents ; Organometallic Compounds ; Phthalazines ; Poly(ADP-ribose) Polymerase Inhibitors ; Radioisotopes ; Radiopharmaceuticals ; Receptors, Somatostatin ; SSTR2 protein, human ; Lutetium (5H0DOZ21UJ) ; talazoparib (9QHX048FRV) ; lutetium Lu 177 dotatate (AE221IM3BB) ; Lutetium-177 (BRH40Y9V1Q) ; Poly(ADP-ribose) Polymerases (EC 2.4.2.30) ; Octreotide (RWM8CCW8GP)
Language	English
Publishing date	2020-06-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-67199-9
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Article ; Online: Navigating the challenge of tumor heterogeneity in cancer therapy.

Fedele, Clare / Tothill, Richard W / McArthur, Grant A

Cancer discovery

2014 Volume 4, Issue 2, Page(s) 146–148

Abstract: The future of cancer treatment lies in personalized strategies designed to specifically target tumorigenic cell populations present in an individual. Although recent advances in directed therapies have greatly improved patient outcomes in some cancers, ... ...

Abstract	The future of cancer treatment lies in personalized strategies designed to specifically target tumorigenic cell populations present in an individual. Although recent advances in directed therapies have greatly improved patient outcomes in some cancers, intuitive drug design is proving more difficult than expected owing largely to the complexity of human cancers. Intratumoral heterogeneity, the presence of multiple genotypically and/or phenotypically distinct cell subpopulations within a single tumor, is a likely cause of drug resistance. Advances in systems biology are helping to unravel the mysteries of cancer progression. In this issue of Cancer Discovery, Zhao and colleagues define a path for functional validation of computational modeling in the context of heterogeneous tumor populations and their potential for drug response and resistance.
MeSH term(s)	Animals ; Female ; Genetic Heterogeneity ; Humans ; Models, Biological ; Neoplasms/genetics
Language	English
Publishing date	2014-02
Publishing country	United States
Document type	Comment ; Journal Article
ZDB-ID	2625242-9
ISSN	2159-8290 ; 2159-8274
ISSN (online)	2159-8290
ISSN	2159-8274
DOI	10.1158/2159-8290.CD-13-1042
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