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A Serum Metabolomics Classifier Derived from Elderly Patients with Metastatic Colorectal Cancer Predicts Relapse in the Adjuvant Setting.

ABSTRACT: Adjuvant treatment for patients with early stage colorectal cancer (eCRC) is currently based on suboptimal risk stratification, especially for elderly patients. Metabolomics may improve the identification of patients with residual micrometastases after surgery. In this retrospective study, we hypothesized that metabolomic fingerprinting could improve risk stratification in patients with eCRC. Serum samples obtained after surgery from 94 elderly patients with eCRC (65 relapse free and 29 relapsed, after 5-years median follow up), and from 75 elderly patients with metastatic colorectal cancer (mCRC) obtained before a new line of chemotherapy, were retrospectively analyzed via proton nuclear magnetic resonance spectroscopy. The prognostic role of metabolomics in patients with eCRC was assessed using Kaplan-Meier curves. PCA-CA-kNN could discriminate the metabolomic fingerprint of patients with relapse-free eCRC and mCRC (70.0% accuracy using NOESY spectra). This model was used to classify the samples of patients with relapsed eCRC: 69% of eCRC patients with relapse were predicted as metastatic. The metabolomic classification was strongly associated with prognosis (p-value 0.0005, HR 3.64), independently of tumor stage. In conclusion, metabolomics could be an innovative tool to refine risk stratification in elderly patients with eCRC. Based on these results, a prospective trial aimed at improving risk stratification by metabolomic fingerprinting (LIBIMET) is ongoing.

SUBMITTER: Di Donato S

PROVIDER: S-EPMC8199587 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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A Serum Metabolomics Classifier Derived from Elderly Patients with Metastatic Colorectal Cancer Predicts Relapse in the Adjuvant Setting.

Di Donato Samantha S Vignoli Alessia A Biagioni Chiara C Malorni Luca L Mori Elena E Tenori Leonardo L Calamai Vanessa V Parnofiello Annamaria A Di Pierro Giulia G Migliaccio Ilenia I Cantafio Stefano S Baraghini Maddalena M Mottino Giuseppe G Becheri Dimitri D Del Monte Francesca F Miceli Elisangela E McCartney Amelia A Di Leo Angelo A Luchinat Claudio C Biganzoli Laura L

Cancers 20210602 11

Adjuvant treatment for patients with early stage colorectal cancer (eCRC) is currently based on suboptimal risk stratification, especially for elderly patients. Metabolomics may improve the identification of patients with residual micrometastases after surgery. In this retrospective study, we hypothesized that metabolomic fingerprinting could improve risk stratification in patients with eCRC. Serum samples obtained after surgery from 94 elderly patients with eCRC (65 relapse free and 29 relapsed ...[more]

PMID: 34199435

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Project description:BackgroundMetastatic colorectal cancer (mCRC) is a highly heterogeneous disease from a clinical, molecular, and immunological perspective. Current predictive models rely primarily in tissue based genetic analysis, which not always correlate with inflammatory response. Here we evaluated the role of a circulating inflammatory signature as a prognostic marker in mCRC.MethodsTwo hundred eleven newly diagnosed patients with mCRC were enrolled in the study. One hundred twenty-one patients had unresectable metastases, whereas ninety patients had potentially resectable liver metastases at presentation. Analysis of miR-21, IL-6, and IL-8 in the plasma of peripheral blood was performed at baseline. Patients with high circulating levels of ≥2 of the three inflammation markers (miR-21, IL-6, and IL-8) were considered to have the "Inflammation phenotype-positive CISIG".ResultsPositive CISIG was found in 39/90 (43%) and 50/121 (45%) patients in the resectable and unresectable cohort, respectively. In the resectable population the median relapse-free survival was 18.4 compared to 31.4 months (p = 0.001 HR 2.09, 95% CI 1.2-3.67) for positive vs. negative CISIG. In contrast, the individual components were not significant. In the same population the median overall survival was 46.2 compared to 66.0 months (p = 0.0003, HR 2.57, 95% CI 1.26-5.27) for positive vs. negative CISIG, but not significant for the individual components. In the unresectable population, the median overall survival was 13.5 compared to 25.0 months (p = 0.0008, HR 2.49, 95% CI 1.46-4.22) for positive vs. negative CISIG. IL-6 was independently prognostic with overall survival of 16.2 compared to 27.0 months (p = 0.004, HR 1.96, 95% CI 1.24-3.11) for high vs. low IL-6, but not the other components. Using a Cox regression model, we demonstrated that CISIG is an independent predictive marker of survival in patients with unresectable disease (HR 1.8, 95% CI 1.2, 2.8, p < 0.01).ConclusionIn two different cohorts, we demonstrated that CISIG is a strong prognostic factor of relapse-free and overall survival of patients with mCRC. Based on these data, analysis of circulating inflammatory signaling can be complimentary to traditional molecular testing.

Project description:BackgroundThe challenge when selecting elderly patients with colorectal cancer (CRC) for adjuvant therapy is to estimate the likelihood that death from other causes will preclude cancer events from occurring. The aim of this paper is to evaluate whether comprehensive geriatric assessment (CGA) can predict survival and cancer-specific mortality in elderly CRC patients candidates for adjuvant therapy.Material and methodsOne hundred ninety-five consecutive patients aged ≥75 with high-risk stage II and stage III CRC were prospectively included from May 2008 to May 2015. All patients underwent CGA, which evaluated comorbidity, polypharmacy, functional status, geriatric syndromes, mood, cognition, and social support. According to CGA results, patients were classified into three groups-fit, medium-fit, and unfit-to receive standard therapy, adjusted treatment, and best supportive care, respectively. We recorded survival and cause of death and used the Fine-Gray regression model to analyze competing causes of death.ResultsFollowing CGA, 85 (43%) participants were classified as fit, 57 (29%) as medium-fit, and 53 (28%) as unfit. The univariate 5-year survival rates were 74%, 52%, and 27%. Sixty-one (31%) patients died due to cancer progression (53%), non-cancer-related cause (46%), and unknown reasons (1%); there were no toxicity-related deaths. Fit and medium-fit participants were more likely to die due to cancer progression, whereas patients classified as unfit were at significantly greater risk of non-cancer-related death.ConclusionCGA showed efficacy in predicting survival and discriminating between causes of death in elderly patients with high-risk stage II and stage III resected CRC, with potential implications for shaping the decision-making process for adjuvant therapies.Implications for practiceAdjuvant therapy in elderly patients with colorectal cancer is controversial due to the high risk for competing events among these patients. In order to effectively select older patients for adjuvant therapy, we have to weigh the risk of cancer-related mortality and the potential survival benefits with treatment against the patient's life expectancy, irrespective of cancer. This prospective study focused on the prognostic value of geriatric assessment for survival using a competing-risk analysis approach, providing an important contribution on the treatment decision-making process and helping clinicians to identify elderly patients who might benefit from adjuvant chemotherapy among those who will not.

Project description:In developed countries, breast cancer (BC) is the most common type of cancer in women, mainly affecting patients over age 60. Due to the increasing life expectancy and population ageing, the incidence of BC is expected to increase significantly in the coming years. However, no standardized clinical guidelines are available to assist in decision-making in elderly patients. Moreover, there is a lack of quality scientific evidence to guide treatment selection in this patient population, who are underrepresented in clinical trials. Consequently, up to 50% of elderly women are treated suboptimally, which implies a worse prognosis and survival. Given that the current estimated life expectancy of a healthy 70-year-old woman is 15 years, any treatment capable of reducing the likelihood of disease recurrence and cancer-specific mortality in this patient population would be beneficial. Adjuvant radiotherapy (RT) is one of the pillars of treatment for BC and it plays a key role in improving local control (LC) and overall survival (OS). Adjuvant RT is clearly indicated in young patients who undergo breast-conserving surgery (BCS) as well as in high risk patients, regardless of age. However, the use of adjuvant RT in older patients with early-stage disease has decreased in recent years-even in patients who undergo BCS-due to outdated concerns about the possible side effects of RT and reports suggesting that RT can be omitted in low-risk patients. One of the greatest challenges currently facing radiation oncologists who specialise in the treatment of BC is the selection of elderly patients who are likely to benefit from adjuvant RT. There is also a clear need to critically evaluate the available evidence and to apply those findings to routine clinical practice. Given this context, the aim of the present review is to clarify the current role of adjuvant RT in the management of BC in older women-particularly those with early-stage disease-and to dispel the myths surrounding the use of RT to treat elderly women. This review primarily focuses on the indications, controversies, and irradiation techniques used in this patient subgroup.

Dataset Information

A Serum Metabolomics Classifier Derived from Elderly Patients with Metastatic Colorectal Cancer Predicts Relapse in the Adjuvant Setting.

Publications

A Serum Metabolomics Classifier Derived from Elderly Patients with Metastatic Colorectal Cancer Predicts Relapse in the Adjuvant Setting.

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