scholarly journals Effect of oxaliplatin plus 5-fluorouracil or capecitabine on circulating and imaging biomarkers in patients with metastatic colorectal cancer: a prospective biomarker study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Reem D. Mahmood ◽  
Danielle Shaw ◽  
Tine Descamps ◽  
Cong Zhou ◽  
Robert D. Morgan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Metastatic Colorectal Cancer ◽  
Targeted Therapies ◽  
Progression Free Survival ◽  
Cytotoxic Chemotherapy ◽  
Imaging Biomarker ◽  
Imaging Biomarkers ◽  
Pre Treatment ◽  
The Impact

Abstract Background Patients with metastatic colorectal cancer are treated with cytotoxic chemotherapy supplemented by molecularly targeted therapies. There is a critical need to define biomarkers that can optimise the use of these therapies to maximise efficacy and avoid unnecessary toxicity. However, it is important to first define the changes in potential biomarkers following cytotoxic chemotherapy alone. This study reports the impact of standard cytotoxic chemotherapy across a range of circulating and imaging biomarkers. Methods A single-centre, prospective, biomarker-driven study. Eligible patients included those diagnosed with colorectal cancer with liver metastases that were planned to receive first line oxaliplatin plus 5-fluorouracil or capecitabine. Patients underwent paired blood sampling and magnetic resonance imaging (MRI), and biomarkers were associated with progression-free survival (PFS) and overall survival (OS). Results Twenty patients were recruited to the study. Data showed that chemotherapy significantly reduced the number of circulating tumour cells as well as the circulating concentrations of Ang1, Ang2, VEGF-A, VEGF-C and VEGF-D from pre-treatment to cycle 2 day 2. The changes in circulating concentrations were not associated with PFS or OS. On average, the MRI perfusion/permeability parameter, Ktrans, increased in response to cytotoxic chemotherapy from pre-treatment to cycle 2 day 2 and this increase was associated with worse OS (HR 1.099, 95%CI 1.01–1.20, p = 0.025). Conclusions In patients diagnosed with colorectal cancer with liver metastases, treatment with standard chemotherapy changes cell- and protein-based biomarkers, although these changes are not associated with survival outcomes. In contrast, the imaging biomarker, Ktrans, offers promise to direct molecularly targeted therapies such as anti-angiogenic agents.

scholarly journals Effect of oxaliplatin plus 5-fluorouracil or capecitabine on circulating and imaging biomarkers in patients with metastatic colorectal cancer: a prospective biomarker study

2020 ◽  
Author(s):  
Reem Mahmood ◽  
Danielle Shaw ◽  
Tine Descamps ◽  
Cong Zhou ◽  
Robert D. Morgan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Metastatic Colorectal Cancer ◽  
Targeted Therapies ◽  
Progression Free Survival ◽  
Cytotoxic Chemotherapy ◽  
Imaging Biomarker ◽  
Imaging Biomarkers ◽  
Pre Treatment ◽  
The Impact

Abstract Background: Patients with metastatic colorectal cancer are treated with cytotoxic chemotherapy supplemented by molecularly targeted therapies. There is a critical need to define biomarkers that can optimise the use of these therapies to maximise efficacy and avoid unnecessary toxicity. However, it is important to first define the changes in potential biomarkers following cytotoxic chemotherapy alone. This study reports the impact of standard cytotoxic chemotherapy across a range of circulating and imaging biomarkers.Methods: A single-centre, prospective, biomarker-driven study. Eligible patients included those diagnosed with colorectal cancer with liver metastases that were planned to receive first line oxaliplatin plus 5-fluorouracil or capecitabine. Patients underwent paired blood sampling and magnetic resonance imaging (MRI), and biomarkers were associated with progression-free survival (PFS) and overall survival (OS).Results: 20 patients were recruited to the study. Data showed that chemotherapy significantly reduced the number of circulating tumour cells as well as the circulating concentrations of Ang1, Ang2, VEGF-A, VEGF-C and VEGF-D from pre-treatment to cycle 2 day 2. The changes in circulating concentrations were not associated with PFS or OS. On average, the MRI perfusion/permeability parameter, Ktrans, increased in response to cytotoxic chemotherapy from pre-treatment to cycle 2 day 2 and this increase was associated with worse OS (HR 1.099, 95%CI 1.01-1.20, p=0.025).Conclusions: In patients diagnosed with colorectal cancer with liver metastases, treatment with standard chemotherapy changes cell- and protein-based biomarkers, although these changes are not associated with survival outcomes. In contrast, the imaging biomarker, Ktrans, offers promise to direct molecularly targeted therapies such as anti-angiogenic agents.

scholarly journals Effect of oxaliplatin plus 5-fluorouracil or capecitabine on circulating and imaging biomarkers in patients with metastatic colorectal cancer: a prospective biomarker study

2020 ◽  
Author(s):  
Reem Mahmood ◽  
Danielle Shaw ◽  
Tine Descamps ◽  
Cong Zhou ◽  
Robert D. Morgan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Metastatic Colorectal Cancer ◽  
Targeted Therapies ◽  
Cytotoxic Chemotherapy ◽  
Imaging Biomarker ◽  
Imaging Biomarkers ◽  
Study Results ◽  
Pre Treatment ◽  
The Impact

Abstract Background: Patients with metastatic colorectal cancer are treated with cytotoxic chemotherapy supplemented by molecularly targeted therapies. There is a critical need to define biomarkers that can optimise the use of these therapies to maximise efficacy and avoid unnecessary toxicity. However, it is important to firstly define the changes in potential biomarkers following cytotoxic chemotherapy alone. This study reports the impact of standard cytotoxic chemotherapy across a range of circulating and imaging biomarkers.Methods: A single-centre, prospective, biomarker-driven study. Eligible patients included those diagnosed with colorectal cancer with liver metastases that were planned to receive first line oxaliplatin plus 5-fluorouracil or capecitabine. Patients underwent paired blood sampling and magnetic resonance imaging (MRI), and biomarkers were associated with progression-free survival (PFS) and overall survival (OS).Results: 20 patients were recruited to the study. Results showed that chemotherapy significantly reduced the number of circulating tumour cells as well as the circulating concentrations of Ang1, Ang2, VEGF-A, VEGF-C and VEGF-D from pre-treatment to cycle 2 day 2. The changes in circulating concentrations were not associated with PFS or OS. Across all patients, the MRI perfusion parameter, Ktrans, increased in response to cytotoxic chemotherapy from pre-treatment to cycle 2 day 2 and this increase was associated with worse OS (HR 1.099, 95%CI 1.01-1.20, p=0.025).Conclusions: In patients diagnosed with colorectal cancer with liver metastases, treatment with standard chemotherapy changes cell- and protein-based biomarkers, although these changes are not associated with survival outcomes. In contrast, the imaging biomarker, Ktrans, offers promise to direct molecular targeted therapies such as anti-angiogenic agents.

Lonsurf (trifluridine/tipiracil): Assessing the impact of dose related toxicities and progression free survival in (refractory) metastatic colorectal cancer

2021 ◽  
pp. 107815522110179
Author(s):  
Olivia R Court
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Dose Reduction ◽  
Progression Free Survival ◽  
Electronic Patient Records ◽  
Free Survival ◽  
Length Of Treatment ◽  
Common Grade ◽  
Grade 3 ◽  
The Impact

In the RECOURSE trial which lead to its accreditation, Lonsurf (trifluridine/tipiracil) was shown to extend progression free survival (PFS) by 1.8 months in metastatic colorectal cancer. This Trust audit aims to assess the average quantity of cycles of Lonsurf received by participants and the length of time it extends PFS. Similarly, to identify how many participants required a dose-reduction or experienced toxicities which necessitated supportive therapies. Quantitative data was collected retrospectively from all participants who had received ≥1 cycle of Lonsurf from The Clatterbridge Cancer Centre (CCC) from 2016 until June 2020. Participant electronic patient records were accessed to identify toxicity grading, length of treatment received, the date progression was identified, if dose reductions were applied and if supportive therapies were administered. Lonsurf extends PFS in patients with metastatic colorectal cancer at CCC by 3.0 months (95% CI: 2.73–3.27) and average treatment length was 2.4 months. However, 78 participants (41.5%) received a dose reduction due to toxicities. A total of 955 toxicities were recorded by participants; the most commonly reported toxicities irrespective of grade were fatigue (33.8%), diarrhoea (13.8%) and nausea (12.3%). The most common grade ≥3 toxicities were constipation and infection. The most frequently utilised supportive therapies were loperamide (49.6%) and domperidone (49.1%). Granulocyte colony stimulating factor (GCSF) was required by patients on 5 occasions (0.3%) in total. Lonsurf extends median PFS in patients with metastatic colorectal cancer by 3.0 months. The most common grade ≥3 toxicities which necessitated supportive therapies or a dose reduction were gastrointestinal and infection.

scholarly journals Treatment with Antiangiogenic Drugs in Multiple Lines in Patients with Metastatic Colorectal Cancer: Meta-Analysis of Randomized Trials

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
R.-D. Hofheinz ◽  
U. Ronellenfitsch ◽  
S. Kubicka ◽  
A. Falcone ◽  
I. Burkholder ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Kinase Inhibitors ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Optimal Sequence ◽  
Primary Endpoints ◽  
Disease Stabilization ◽  
Antiangiogenic Drugs ◽  
The Impact

Background. In metastatic colorectal cancer (mCRC), continuing antiangiogenic drugs beyond progression might provide clinical benefit. We synthesized the available evidence in a meta-analysis.Patients and Methods. We conducted a meta-analysis of studies investigating the use of antiangiogenic drugs beyond progression. Eligible studies were randomized phase II/III trials. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints were the impact of continuing antiangiogenic drugs (i) in subgroups, (ii) in different types of compounds targeting the VEGF-axis (monoclonal antibodies versus tyrosine kinase inhibitors), and (iii) on remission rates and prevention of progression.Results. Eight studies (3,668 patients) were included. Continuing antiangiogenic treatment beyond progression significantly improved PFS (HR 0.64; 95%-CI, 0.55–0.75) and OS (HR 0.83; 95%-CI, 0.76–0.89). PFS was significantly improved in all subgroups with comparable HR. OS was improved in all subgroups stratified by age, gender, and ECOG status. The rate of patients achieving at least stable disease was improved with an OR of 2.25 (95%-CI, 1.41–3.58).Conclusions. This analysis shows a significant PFS and OS benefit as well as a benefit regarding disease stabilization when using antiangiogenic drugs beyond progression in mCRC. Future studies should focus on the optimal sequence of administering antiangiogenic drugs.

scholarly journals Clinical and molecular determinants of extrahepatic disease progression in patients with metastatic colorectal cancer with liver-limited metastases deemed initially unresectable

ESMO Open ◽  
2019 ◽  
Vol 4 (2) ◽  
pp. e000496
Author(s):  
Elena Ongaro ◽  
Chiara Cremolini ◽  
Daniele Rossini ◽  
Francesca Corti ◽  
Filippo Pagani ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Metastatic Colorectal Cancer ◽  
Disease Progression ◽  
Progression Free Survival ◽  
Extrahepatic Disease ◽  
Nodal Involvement ◽  
Liver Resections ◽  
Multicentre Cohort Study ◽  
Molecular Determinants

BackgroundNo tools to predict the probability of extrahepatic disease progression (ePD) of initially unresectable, liver-limited metastatic colorectal cancer (mCRC) are currently available. To estimate the likelihood to develop ePD and to identify clinical and molecular factors that could predict extrahepatic progression-free survival (ePFS), we conducted an observational, retrospective, multicentre cohort study.MethodsWe retrospectively identified a cohort of 225 patients with initially unresectable liver-limited disease (LLD), treated from January 2004 to December 2017 with first-line doublets or triplet plus a biological agent at two Italian institutions.Results173 (77%) patients experienced ePD which occurred within 1, 2 or 3 years from the diagnosis of mCRC in 15%, 49% and 66% of patients, respectively. Globally, 164 (73%) patients underwent a liver resection at some point of their disease history, and 54 (33%) of them underwent a subsequent locoregional treatment. Age > 70 years, locoregional nodal involvement at diagnosis of colorectal cancer and ≥4 liver metastases were significantly associated with higher risk of ePD while liver resections were associated with reduced risk of ePD. In the multivariable model, number of liver metastases (subdistribution HR, SHR 1.63, 95% CI 1.12 to 2.36; p = 0.01) and liver resections (SHR 0.43, 95% CI 0.29 to 0.63; p = 0.001) were still associated with ePD. Number of liver metastases < 4, no nodal involvement at diagnosis and liver resections were also associated with prolonged ePFS.ConclusionsThe identified clinical factors could help physicians in personalising the intensity and aggressiveness of liver-directed treatments in patients with mCRC with initially unresectable LLD.

What is the benefit for patients suffering from metastatic colorectal cancer (mCRC) after bevacizumab-based regimen (BBR), cetuximab-based regimen (CBR), and panitumumab (P)?

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 595-595
Author(s):  
J. Metges ◽  
J. Ramée ◽  
J. Raoul ◽  
A. Gourlaouen ◽  
M. Porneuf ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Targeted Therapies ◽  
Primary Tumor ◽  
Progression Free Survival ◽  
Tumor Site ◽  
Primary Tumor Site ◽  
Health Politics ◽  
Private And Public

595 Background: Metastatic colorectal cancer (mCRC) management has been clearly improved by targeted therapies such as anti VEGF and /or anti-HER1 drugs. The evaluation of the use of targeted therapies in the real world is strategic to assess health politics. OMIT Bretagne-Pays de la Loire is a network of private and public cancer centers that has been leading cohort studies evaluating Folfiri-bevacizumab treatment, the cost of targeted therapies and the succession of targeted therapies. Methods: The purpose of this study is to evaluate the benefit and safety of three consecutive targeted therapies in patients with KRAS wild-type unresectable mCRC. Sex, age, localization of the primary tumor site, successive chemotherapeutic regimens, toxicities, response rates, progression free survival and overall survival have been studied. Results: 34 patients (22 men, 12 women, median age 63 years [43-82]) have been prospectively recruited between 2003 and 2010. All of them received bevacizumab specially in association with FOLFIRI, cetuximab in association with irinotecan, panitumumab as monotherapy and others chemotherapies than FOLFOX, FOLFIRI, XELOX. The primary tumor site was colon (71%), junction (5%), and rectum (24%). 22 patients had metastatic colorectal tumor, 28 were operated on their primary tumor and 12 underwent resection after one line of treatment. Patients received successively 3 to 8 different lines of treatment for progressive mCRC. Toxicities of targeted therapies were manageable. Objective responses were observed in 38% (13) of the patients treated with BBR, 37% (11) treated with CBR and 25% (6) treated with P. Disease stabilization was achieved in 32% (11) of the patients treated with BBR, in 10% (3) with CBR and in 8% (2) with P. PFS at 80 months is 15%. Median OS from first metastatic line at death was 47.43 months (24.23-70.84). PFS and OS curves will be shown during the meeting. Conclusions: Our study clearly shows that patients receiving successively the three schedules (BBR, CBR, P) have a high overall survival with manageable side effects. No significant financial relationships to disclose.

Use and impact of bevacizumab in patients undergoing liver resection for metastatic colorectal cancer in routine clinical practice.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 698-698
Author(s):  
Edmond Michael Kwan ◽  
Belinda Lee ◽  
Hui-Li Wong ◽  
Margaret Lee ◽  
Rachel Wong ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Resection ◽  
Liver Metastases ◽  
Metastatic Colorectal Cancer ◽  
Survival Outcomes ◽  
Perioperative Chemotherapy ◽  
Palliative Intent ◽  
Clinical Dilemma ◽  
The Impact ◽  
Proven Benefit

698 Background: In metastatic colorectal cancer (mCRC) patients with isolated liver metastases, surgical resection offers the greatest likelihood of cure. Whilst for mCRC patients treated with palliative intent the addition of bevacizumab to the chemotherapy backbone is of proven benefit, whether to use bevacizumab in the resectable or potentially resectable population is a clinical dilemma. Methods: Consecutive patients who underwent resection of liver metastases were identified from a prospective Australian mCRC registry that captures comprehensive data on patient and tumor characteristics (including resectability), treatment and outcome. The use of bevacizumab in this setting was examined and the impact on outcomes was explored. Results: From a total mCRC population of 1,700 patients, 543 patients with liver-only mCRC were identified, of which 217 patients (40%) underwent liver resection. Perioperative chemotherapy was administered to 185 patients (85.3%), with bevacizumab added to chemotherapy in 73 (39.5%) patients. There was a trend for bevacizumab treated patients to be younger (median age 60.4 vs 65.1 years, p = 0.07) and fitter (mean Charlson score 2.22 vs 2.64, p = 0.054). Patients that received bevacizumab with perioperative chemotherapy were considerably less likely to have disease regarded as resectable at diagnosis (39 of 73 (53.4%) vs 95 of 112 (84.8%), p =<.01). At 5 years, overall survival was similar for bevacizumab treated and non-treated patients (61.4% vs. 59.2%, HR 0.83, p=0.52). There were no deaths within 30 days of surgery in any patients. Conclusions: Despite limited evidence to support the use of bevacizumab in patients with resectable or potentially resectable liver-only mCRC, clinicians are not infrequently utilising this approach, particularly in younger and fitter patients and those not considered to have resectable disease at diagnosis. The addition of bevacizumab did not appear to impact survival outcomes. A multivariate analysis is underway to better define the impact of bevacizumab on survival outcomes.

scholarly journals Image Contrast, Image Pre-Processing, and T1 Mapping Affect MRI Radiomic Feature Repeatability in Patients with Colorectal Cancer Liver Metastases

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 240
Author(s):  
Damien J. McHugh ◽  
Nuria Porta ◽  
Ross A. Little ◽  
Susan Cheung ◽  
Yvonne Watson ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Intraclass Correlation ◽  
Imaging Biomarkers ◽  
Sequence Comparisons ◽  
Colorectal Cancer Liver Metastases ◽  
T1 And T2 ◽  
Non Gaussian ◽  
The Impact ◽  
T2 Weighted Images

Imaging biomarkers require technical, biological, and clinical validation to be translated into robust tools in research or clinical settings. This study contributes to the technical validation of radiomic features from magnetic resonance imaging (MRI) by evaluating the repeatability of features from four MR sequences: pre-contrast T1- and T2-weighted images, pre-contrast quantitative T1 maps (qT1), and contrast-enhanced T1-weighted images. Fifty-one patients with colorectal cancer liver metastases were scanned twice, up to 7 days apart. Repeatability was quantified using the intraclass correlation coefficient (ICC) and repeatability coefficient (RC), and the impact of non-Gaussian feature distributions and image normalisation was evaluated. Most radiomic features had non-Gaussian distributions, but Box–Cox transformations enabled ICCs and RCs to be calculated appropriately for an average of 97% of features across sequences. ICCs ranged from 0.30 to 0.99, with volume and other shape features tending to be most repeatable; volume ICC > 0.98 for all sequences. 19% of features from non-normalised images exhibited significantly different ICCs in pair-wise sequence comparisons. Normalisation tended to increase ICCs for pre-contrast T1- and T2-weighted images, and decrease ICCs for qT1 maps. RCs tended to vary more between sequences than ICCs, showing that evaluations of feature performance depend on the chosen metric. This work suggests that feature-specific repeatability, from specific combinations of MR sequence and pre-processing steps, should be evaluated to select robust radiomic features as biomarkers in specific studies. In addition, as different repeatability metrics can provide different insights into a specific feature, consideration of the appropriate metric should be taken in a study-specific context.

Response to PD-1 and PD-L1 based immunotherapy in MSS advanced colorectal cancer is impacted by metastatic disease sites.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 72-72
Author(s):  
Marwan Fakih ◽  
Jaideep Singh Sandhu ◽  
Chongkai Wang ◽  
Ching Ouyang
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Disease Control ◽  
Metastatic Disease ◽  
Cox Regression ◽  
Lung Metastases ◽  
Therapy Response ◽  
Progression Free Survival ◽  
Liver Involvement ◽  
The Impact

72 Background: Microsatellite stable (MSS) metastatic colorectal cancer (mCRC) has been associated with immunotherapy resistance. However, the impact of metastatic diseases sites on clinical outcome with checkpoint inhibition has not be adequately investigated. Methods: Following IRB approval (14361), we performed a retrospective study to assess the response and progression-free survival (PFS) to PD-1 or PD-L1 based therapy in patients with MSS mCRC who progressed following standard chemotherapy and targeted therapy. Patients were included if they received an FDA approved anti-PD1 or anti-PD-L1 agent, alone or in combination with other investigational agents. Exclusion criteria included concurrent cytotoxic therapy. Response and PFS were determined by RECIST guidelines. Results: 97 patients with refractory MSS mCRC satisfied the inclusion criteria were evaluable for analysis. 57, 17, 13, and 10 received nivolumab, atezolizumab, pembrolizumab, and durvalumab, respectively. 47, 8, 10, 10, 17 received concurrent VEGFR, MEK, CTLA-4, radiation, or other targeted therapies. Among tested variables, including age, gender, primary tumor location, ECOG status, RAS, BRAF, APC, TP53, TMB, and sites of metastasis, only ECOG status (0 vs. 1) and metastatic disease to the liver were associated with disease control (partial response and stable disease; p = 0.005 and < 0.001 respectively). Disease control rates in patients without liver metastases (n = 43) was 56% (95% CI: 40-71%), compared with 2% (95% CI: 0.1-10%) in patients with liver metastases (n = 54) (p < 0.001). Also, liver involvement was predictive for PFS based on multivariate Cox regression model (p < 0.001). The median PFS in patients with liver involvement was 1.5 vs 4.5 months for no liver involvement (HR = 4.41, p = < 0.001). Amongst patients without liver metastases, 35% (15/43) remained without progression at 6 months. These patients were characterized by lung metastases (n = 8) and/or lymph node metastases (n = 4). Conclusions: The presence of liver metastases is MSS mCRC is predictive for lack of benefit from PD-1/PD-L1 inhibitors. Patients without liver metastases can derive a meaningful clinical benefit, with 35% being progression-free at 6 months. Future PD-1/PD-L1 drug development should consider metastatic sites of disease in study design and development.

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