Abstract 5104
Background
Adjuvant treatment decisions for pts with eCRC are currently based on suboptimal risk stratification factors, especially for elderly pts. Metabolomics measures multiple cancer-related metabolites with potential to identify new biomarkers in this setting. We have shown that serum metabolomics can discriminate pts with eCRC from pts with metastatic CRC (mCRC). We hypothesized that a metabolomic score derived from pts with mCRC may identify pts with eCRC with an increased risk of relapse. This hypothesis was tested in a cohort of elderly pts with eCRC.
Methods
Serum samples from 103 pts aged ≥70 were collected from four clinical trials with 5 years follow up. These samples were derived from 55 pts with eCRC, and 48 with mCRC. Samples were retrospectively analyzed via proton nuclear magnetic resonance (1H NMR), to assess their metabolomic fingerprints. A Random Forest (RF) classification model was built using a training set of 30 eCRC pts free from relapse at 5 years and all mCRC pts (N = 48). This model was then applied to a validation set constituted by the remaining eCRC pts (10 relapse-free and 15 relapsed). A risk-of-recurrence score was built on the basis of the likelihood of the sample being misclassified as metastatic.
Results
In the eCRC group, 44% (n = 24) received adjuvant chemotherapy, and 27% (n = 15) experienced relapse. In the training set, the RF model discriminated eCRC from mCRC with an accuracy of 74.4%. The RF risk of recurrence score correlated with relapse, with an AUC of 0.754 in ROC analysis. In the training set, by maximizing specificity and sensitivity, a threshold for the RF score was set at 0.55. In the validation set, using this threshold, an AUC of 0.727 in ROC analysis, and a prediction accuracy of 76% (73.3% sensitivity, 80% specificity) were obtained in predicting relapse.
Conclusions
Serum metabolomics performed on post-operative samples of elderly pts with eCRC identifies pts with higher risk of relapse with good accuracy. This may represent a tool to refine risk stratification in this population, to maximize the benefit from adjuvant chemotherapy. Based on these results, a prospective trial is ongoing (LIquid BIopsy and METabolomics in CRC - LIBIMET).
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Fondazione Sandro Pitigliani per la Lotto Contro i Tumori - ONLUS.
Disclosure
S. Di Donato: Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Advisory / Consultancy, Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Servier; Travel / Accommodation / Expenses: Celgene; Advisory / Consultancy, Travel / Accommodation / Expenses: Sanofi; Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer. E. Mori: Travel / Accommodation / Expenses: Bayer. L. Malorni: Honoraria (self): AstraZeneca; Advisory / Consultancy: Novartis; Travel / Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Pfizer; Travel / Accommodation / Expenses: Roche. D. Becheri: Travel / Accommodation / Expenses: Daiichi-Sankyo; Travel / Accommodation / Expenses: Bristol-Myers Squibb. A. Di Leo: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Celgene; Advisory / Consultancy, Travel / Accommodation / Expenses: Daiichi-Sankyo; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Eisai; Advisory / Consultancy: Genentech; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Genomic Health; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre; Advisory / Consultancy, Travel / Accommodation / Expenses: Puma Biotechnology; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche. L. Biganzoli: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Astrazeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Celgene; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Eisai; Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Genomic Health; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Ipsen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche. All other authors have declared no conflicts of interest.
Resources from the same session
3353 - Results of the 3rd interim analysis of C-Patrol: A non-interventional study on olaparib in German routine clinical practice
Presenter: Jalid Sehouli
Session: Poster Display session 2
Resources:
Abstract
740 - A real-world analysis of the treatment of advanced ovarian cancer with PARPIs
Presenter: Alejandra Martinez de Pinillos
Session: Poster Display session 2
Resources:
Abstract
5867 - Incidence of tumour BRCA1/2 variants in relapsed, platinum-sensitive ovarian, fallopian tube and primary peritoneal cancer
Presenter: Robert Morgan
Session: Poster Display session 2
Resources:
Abstract
2966 - Frequency of mutations in 21 hereditary breast and ovarian cancer susceptibility genes among 882 high-risk individuals
Presenter: Jihong Liu
Session: Poster Display session 2
Resources:
Abstract
1687 - BRCA testing of 1,284 Brazilian patients for hereditary breast and ovarian cancer in a routine diagnostic setting
Presenter: Fernanda Milanezi
Session: Poster Display session 2
Resources:
Abstract
3162 - A multi-center integrative study on cancer predisposition genes in Chinese patients with epithelial ovarian carcinoma
Presenter: Changbin Zhu
Session: Poster Display session 2
Resources:
Abstract
5993 - Incidental Early Occult Ovarian Cancer after Risk-Reducing Salpingo-Oophorectomy in BRCA1/2 Mutation Carriers followed in a Community Public Hospital
Presenter: Begona Grana Suarez
Session: Poster Display session 2
Resources:
Abstract
5334 - Response to chemotherapy in ovarian cancer (OC) patients with or without prior breast cancer (BC), stratified by BRCA mutation (BRCAm) status
Presenter: Angela George
Session: Poster Display session 2
Resources:
Abstract
4565 - Advanced ovarian cancer: is residual disease after debulking surgery affected by genetics factors involved in angiogenesis and immunity pathways?
Presenter: Michele Bartoletti
Session: Poster Display session 2
Resources:
Abstract
3251 - Surrogate endpoint of progression-free (PFS) and overall survival (OS) for advanced ovarian cancer (AOC) patients (pts) treated with neo-adjuvant chemotherapy (NACT): Results of the CHIVA randomized phase II GINECO study
Presenter: Fabrice Lecuru
Session: Poster Display session 2
Resources:
Abstract