Discovery and Evaluation of Protein Biomarkers as a Signature of Wellness in Late-Stage Cancer Patients in Early Phase Clinical Trials
AuthorsGeary, Bethany; orcid: 0000-0002-5592-5532; email: firstname.lastname@example.org
Peat, Erin; email: email@example.com
Dransfield, Sarah; email: firstname.lastname@example.org
Cook, Natalie; orcid: 0000-0003-2606-1082; email: email@example.com
Thistlethwaite, Fiona; orcid: 0000-0002-4832-7008; email: firstname.lastname@example.org
Graham, Donna; email: email@example.com
Carter, Louise; email: firstname.lastname@example.org
Hughes, Andrew; email: Andrew.email@example.com
Krebs, Matthew G.; email: firstname.lastname@example.org
Whetton, Anthony D.; orcid: 0000-0002-1098-3878; email: email@example.com
MetadataShow full item record
AbstractTARGET (tumour characterisation to guide experimental targeted therapy) is a cancer precision medicine programme focused on molecular characterisation of patients entering early phase clinical trials. Performance status (PS) measures a patient’s ability to perform a variety of activities. However, the quality of present algorithms to assess PS is limited and based on qualitative clinician assessment. Plasma samples from patients enrolled into TARGET were analysed using the mass spectrometry (MS) technique: sequential window acquisition of all theoretical fragment ion spectra (SWATH)-MS. SWATH-MS was used on a discovery cohort of 55 patients to differentiate patients into either a good or poor prognosis by creation of a Wellness Score (WS) that showed stronger prediction of overall survival (p = 0.000551) compared to PS (p = 0.001). WS was then tested against a validation cohort of 77 patients showing significant (p = 0.000451) prediction of overall survival. WS in both sets had receiver operating characteristic curve area under the curve (AUC) values of 0.76 (p = 0.002) and 0.67 (p = 0.011): AUC of PS was 0.70 (p = 0.117) and 0.55 (p = 0.548). These signatures can now be evaluated further in larger patient populations to assess their utility in a clinical setting.
CitationCancers, volume 13, issue 10, page e2443
DescriptionFrom MDPI via Jisc Publications Router
History: accepted 2021-05-12, pub-electronic 2021-05-18
Publication status: Published
Funder: Bloodwise; Grant(s): 19007
Funder: Medical Research Council; Grant(s): MR/M008959/1
Funder: Cancer Research UK; Grant(s): C5759/A25254, A20465
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Is the Morphological Subtype of Extra-Pulmonary Neuroendocrine Carcinoma Clinically Relevant?Frizziero, Melissa; email: firstname.lastname@example.org; Durand, Alice; orcid: 0000-0002-0193-9058; email: email@example.com; Taboada, Rodrigo G.; orcid: 0000-0001-5674-2669; email: firstname.lastname@example.org; Zaninotto, Elisa; email: email@example.com; Luchini, Claudio; orcid: 0000-0003-4901-4908; email: firstname.lastname@example.org; Chakrabarty, Bipasha; email: email@example.com; Hervieu, Valérie; email: firstname.lastname@example.org; Claro, Laura C. L.; email: email@example.com; Zhou, Cong; orcid: 0000-0002-6938-4685; email: firstname.lastname@example.org; Cingarlini, Sara; email: email@example.com; et al. (MDPI, 2021-08-18)Extra-pulmonary neuroendocrine carcinomas (EP-NECs) are lethal cancers with limited treatment options. Identification of contributing factors to the observed heterogeneity of clinical outcomes within the EP-NEC family is warranted, to enable identification of effective treatments. A multicentre retrospective study investigated potential differences in “real-world” treatment/survival outcomes between small-cell (SC) versus (vs.) non-SC EP-NECs. One-hundred and seventy patients were included: 77 (45.3%) had SC EP-NECs and 93 (54.7%) had non-SC EP-NECs. Compared to the SC subgroup, the non-SC subgroup had the following features: (1) a lower mean Ki-67 index (69.3% vs. 78.7%; p = 0.002); (2) a lower proportion of cases with a Ki-67 index of ≥55% (73.9% vs. 88.7%; p = 0.025); (3) reduced sensitivity to first-line platinum/etoposide (objective response rate: 31.6% vs. 55.1%, p = 0.015; and disease control rate; 59.7% vs. 79.6%, p = 0.027); (4) worse progression-free survival (PFS) (adjusted-HR = 1.615, p = 0.016) and overall survival (OS) (adjusted-HR = 1.640, p = 0.015) in the advanced setting. Within the advanced EP-NEC cohort, subgroups according to morphological subtype and Ki-67 index (55% vs. ≥55%) had significantly different PFS (adjusted-p = 0.021) and OS (adjusted-p = 0.051), with the non-SC subgroup with a Ki-67 index of 55% and non-SC subgroup with a Ki-67 index of ≥55% showing the best and worst outcomes, respectively. To conclude, the morphological subtype of EP-NEC provides complementary information to the Ki-67 index and may aid identification of patients who could benefit from alternative first-line treatment strategies to platinum/etoposide.
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