scholarly journals Impact of Variability in Portal Venous Phase Acquisition Timing in Tumor Density Measurement and Treatment Response Assessment: Metastatic Colorectal Cancer as a Paradigm

2017 ◽  
pp. 1-8 ◽  
Author(s):  
Laurent Dercle ◽  
Lin Lu ◽  
Philip Lichtenstein ◽  
Hao Yang ◽  
Deling Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Quality Control ◽  
Metastatic Colorectal Cancer ◽  
Imaging Biomarkers ◽  
Portal Venous Phase ◽  
Computed Tomography Images ◽  
Choi Criteria ◽  
Computer Aided ◽  
Venous Phase ◽  
The Mean

Purpose New response patterns to anticancer drugs have led tumor size–based response criteria to shift to also include density measurements. Choi criteria, for instance, categorize antiangiogenic therapy response as a decrease in tumor density > 15% at the portal venous phase (PVP). We studied the effect that PVP timing has on measurement of the density of liver metastases (LM) from colorectal cancer (CRC). Methods Pretreatment PVP computed tomography images from 291 patients with LM-CRC from the CRYSTAL trial (Cetuximab Combined With Irinotecan in First-Line Therapy for Metastatic Colorectal Cancer; ClinicalTrials.gov identifier: NCT00154102) were included. Four radiologists independently scored the scans’ timing according to a three-point scoring system: early, optimal, late PVP. Using this, we developed, by machine learning, a proprietary computer-aided quality-control algorithm to grade PVP timing. The reference standard was a computer-refined consensus. For each patient, we contoured target liver lesions and calculated their mean density. Results Contrast-product administration data were not recorded in the digital imaging and communications in medicine headers for injection volume (94%), type (93%), and route (76%). The PVP timing was early, optimal, and late in 52, 194, and 45 patients, respectively. The mean (95% CI) accuracy of the radiologists for detection of optimal PVP timing was 81.7% (78.3 to 85.2) and was outperformed by the 88.6% (84.8 to 92.4) computer accuracy. The mean ± standard deviation of LM-CRC density was 68 ± 15 Hounsfield units (HU) overall and 59.5 ± 14.9 HU, 71.4 ± 14.1 HU, 62.4 ± 12.5 HU at early, optimal, and late PVP timing, respectively. LM-CRC density was thus decreased at nonoptimal PVP timing by 14.8%: 16.7% at early PVP ( P < .001) and 12.6% at late PVP ( P < .001). Conclusion Nonoptimal PVP timing should be identified because it significantly decreased tumor density by 14.8%. Our computer-aided quality-control system outperformed the accuracy, reproducibility, and speed of radiologists’ visual scoring. PVP-timing scoring could improve the extraction of tumor quantitative imaging biomarkers and the monitoring of anticancer therapy efficacy at the patient and clinical trial levels.

The impact of cumulative toxicity on physical quality of life in patients with metastatic colorectal cancer receiving first line chemotherapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3564-3564 ◽  
Author(s):  
Claudia Schuurhuizen ◽  
Inge Konings ◽  
Annemarie Braamse ◽  
Laurien Buffart ◽  
Haiko Bloemendal ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
First Line ◽  
Physical Quality ◽  
Cumulative Toxicity ◽  
The Mean ◽  
Grade 3 ◽  
Line Chemotherapy

3564 Background: We have previously suggested that treatment related toxicity has impact on physical quality of life (QOL) scores, as opposed to global QOL. Moreover, the cumulative effect of experienced toxicities, including low-grades AEs, may be of more importance. The purpose of this observational cohort study was to evaluate the association between cumulative toxicity and physical and global QOL in patients with metastatic colorectal cancer (mCRC) receiving chemotherapy. Methods: 105 patients with mCRC starting first line chemotherapy were evaluated. All patients completed the EORTC-QLQ-C30 questionnaire at baseline and after 10 weeks. Toxicity, clinical outcomes and demographics were retrieved from patient records. For each patient, we calculated cumulative toxicity in three different ways: i) total number of adverse events (AEs) (all grades), ii) total number of grade 3-4 AEs, and iii) total number of AEs multiplied by their grade. The relation between each cumulative toxicity score and QOL assessed at 10 weeks, was studied. Results: The mean age of patients was 64.8 ± 9.7 years, 70.5% were male, and 83.8% received first line oxaliplatin based combination chemotherapy. AEs occurred in 98.1% of patients, grade 3-4 AEs in 37.1%, and grade 1-2 AEs in 61.0%. The mean number of experienced AEs (all grades) was 5.3 ± 2.7. The most common toxicities included diarrhea, neuropathy and fatigue. None of the toxicity scores was related to global QOL outcome. A higher total number of all grades AEs (β = - 2.2, 95%CI = -3.7; -6.6) and total number of AEs multiplied by grade (β = -1.3, 95%CI = -2.2; -3.5) were significantly associated with worse physical QOL. Conclusions: Cumulative toxicity, defined as the total of all grades AEs, significantly affects physical QOL in patients with mCRC receiving first line chemotherapy. Improvement of treatment related toxicity management by reducing the total number of AEs, may result in relevant improvements in patients’ QOL. Our results emphasize that future RCTs should present physical QOL outcomes instead of global QOL, as well as all grades and total number of toxicities for individual patients.

Real-world study of cetuximab used every other week versus weekly in US patients with metastatic colorectal cancer (mCRC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15087-e15087 ◽  
Author(s):  
Francois-Xavier Lamy ◽  
Michael Batech ◽  
Shaista Salim ◽  
Emmanuelle Boutmy ◽  
Chris Pescott ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Proportional Hazards ◽  
Cox Model ◽  
Cox Proportional Hazards ◽  
Patient Death ◽  
Claims Database ◽  
Proportional Hazards Regression ◽  
The Mean

e15087 Background: After an initial dose of 400 mg/m², cetuximab (CET) at a dose of 250 mg/m² in combination with chemotherapy (CT) is approved for once-weekly (q1w) use in the treatment of RAS wild-type metastatic colorectal cancer (mCRC). However, off-label use of CET 500 mg/m2 administered every other week (q2w) has been observed in clinical practice. This study aimed to test the noninferiority of q2w vs q1w administration on overall survival (OS) using US claims data. Methods: Using IBM MarketScan, a large US insurance claims database, a cohort of patients with mCRC treated with CET + CT between 2010 and 2016 was identified and classified as q1w or q2w based on observed infusion patterns. The initial CET prescription was defined as the index date, and patient death was determined using a previously published algorithm. Confounding was accounted for using high-dimensional propensity scoring (hdPS) methodology with inverse probability of treatment weighting (IPTW). OS for both groups was compared using Cox proportional hazards regression. Confounders that remained imbalanced after hdPS with IPTW were added to the Cox model. The noninferiority of the q2w regimen was tested with a margin hazard ratio (HR) of 1.25 for q2w vs q1w. Results: 2,869 patients with mCRC exposed to CET were identified of which 1,865 (65.0%) and 1,004 (35.0%) were classified in the q1w and q2w groups, respectively. The mean age of patients was 60.1±11.7 years for q1w and 58.1±11.1 years for q2w. Most patients were male: 57.5% and 60.8% in q1w and q2w, respectively. Approximately 70% of patients in both groups had received prior treatment for mCRC. The most frequently used CT with CET was irinotecan based (64.5% in q1w and 76.5% in q2w). There were 1,628 deaths observed during follow-up (56.7%). After hdPS with IPTW adjustment, differences remained in associated CT (standardized difference <0.25). Crude HR for OS was 1.05 (95% CI, 0.94-1.18), and adjusted HR for OS was 1.04 (95% CI, 0.93-1.17). The inferiority hypothesis was rejected at p<0.001. Conclusions: In this large US claims database, when assessing OS, the q2w administration schedule was found to be noninferior to the q1w schedule in patients with mCRC.

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 ◽  
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.

scholarly journals Comparative effectiveness of chemotherapy in elderly patients with metastatic colorectal cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 463-463
Author(s):  
Sacha Satram-Hoang ◽  
Devi Ramanan ◽  
Luen F. Lee ◽  
Shui Yu ◽  
Carolina M. Reyes ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Real World ◽  
Cox Regression ◽  
Cohort Analysis ◽  
Clinical Trial Data ◽  
Chemotherapeutic Agents ◽  
Duration Of Treatment ◽  
Risk Of Death ◽  
The Mean

463 Background: The management of metastatic colorectal cancer (mCRC) has evolved considerably with advances in chemotherapeutic agents that have led to improved outcomes. Less is known about the benefits of newer agents in the real-world setting. The objective of this study was to evaluate treatment patterns and survival in older, demographically diverse mCRC patients. Methods: Using the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we conducted a retrospective cohort analysis of 5931 stage IIIB, IIIC and IV CRC patients diagnosed between 1/1/ 2000 – 12/31/2007, who were >66 years, enrolled in Medicare Parts A and B, and received first-line treatment with 5FU/LV (n=2907), CAP (capecitabine; n=963), FOLFOX (n=1856) or CAPOX (CAP + oxaliplatin; n=205). Date of last follow-up was 12/31/2009. Statistical comparisons were made between 5FU/LV vs. CAP and FOLFOX vs. CAPOX. Cox regression with backward elimination estimated the relative risk of death, adjusting for demographic and clinical factors. Results: Compared to 5FU/LV, patients treated with CAP were older (>80 years) at diagnosis (36% vs. 22%; p<.0001) and more likely female (59% vs. 53%; p=.0025), while patients receiving CAPOX were older (>80 years: 12% vs 8%; p<0.05) compared to FOLFOX. The mean time to chemotherapy initiation after diagnosis was similar between CAP and 5FU/LV (76 vs. 71 days) and between FOLFOX and CAPOX (75 vs. 70 days). The mean duration of treatment was longer for 5FU/LV (144 days) vs. CAP (122 days; p<.0001) and comparable between CAPOX (144 days) and FOLFOX (150 days; p=0.2139). The incidence of adverse events (AE) within 180 days after initiation of treatment were higher in patients treated with 5FU/LV (37%) vs. CAP (9%); p<.0001 and in FOLFOX (58%) vs. CAPOX (44%); p<0.0001. In multivariate analysis there were no significant differences in risk of death between CAP and 5FU/LV, and between CAPOX and FOLFOX ( table ). Conclusions: Overall survival was comparable between CAP and 5FU/LV and between CAPOX and FOLFOX with fewer AEs associated with CAP and CAPOX. This provides real-world confirmation of clinical trial data. [Table: see text]

scholarly journals Radiomics Response Signature for Identification of Metastatic Colorectal Cancer Sensitive to Therapies Targeting EGFR Pathway

2020 ◽  
Vol 112 (9) ◽  
pp. 902-912 ◽  
Author(s):  
Laurent Dercle ◽  
Lin Lu ◽  
Lawrence H Schwartz ◽  
Min Qian ◽  
Sabine Tejpar ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Computed Tomography ◽  
Metastatic Colorectal Cancer ◽  
Cox Regression ◽  
Surrogate Marker ◽  
Treatment Quality ◽  
Imaging Biomarkers ◽  
Mutational Status ◽  
Radiomics Signature ◽  
Treatment Sensitivity

Abstract Background The authors sought to forecast survival and enhance treatment decisions for patients with liver metastatic colorectal cancer by using on-treatment radiomics signature to predict tumor sensitiveness to irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) alone (F) or in combination with cetuximab (FC). Methods We retrospectively analyzed 667 metastatic colorectal cancer patients treated with F or FC. Computed tomography quality was classified as high (HQ) or standard (SD). Four datasets were created using the nomenclature (treatment) – (quality). Patients were randomly assigned (2:1) to training or validation sets: FCHQ: 78:38, FCSD: 124:62, FHQ: 78:51, FSD: 158:78. Four tumor-imaging biomarkers measured quantitative radiomics changes between standard of care computed tomography scans at baseline and 8 weeks. Using machine learning, the performance of the signature to classify tumors as treatment sensitive or treatment insensitive was trained and validated using receiver operating characteristic (ROC) curves. Hazard ratio and Cox regression models evaluated association with overall survival (OS). Results The signature (area under the ROC curve [95% confidence interval (CI)]) used temporal decrease in tumor spatial heterogeneity plus boundary infiltration to successfully predict sensitivity to antiepidermal growth factor receptor therapy (FCHQ: 0.80 [95% CI = 0.69 to 0.94], FCSD: 0.72 [95% CI = 0.59 to 0.83]) but failed with chemotherapy (FHQ: 0.59 [95% CI = 0.44 to 0.72], FSD: 0.55 [95% CI = 0.43 to 0.66]). In cetuximab-containing sets, radiomics signature outperformed existing biomarkers (KRAS-mutational status, and tumor shrinkage by RECIST 1.1) for detection of treatment sensitivity and was strongly associated with OS (two-sided P &lt; .005). Conclusions Radiomics response signature can serve as an intermediate surrogate marker of OS. The signature outperformed known biomarkers in providing an early prediction of treatment sensitivity and could be used to guide cetuximab treatment continuation decisions.

scholarly journals Application study of the EQ-5D-5L in oncology: linking self-reported quality of life of patients with advanced or metastatic colorectal cancer to clinical data from a German tumor registry

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Kathrin Borchert ◽  
Christian Jacob ◽  
Natalie Wetzel ◽  
Martina Jänicke ◽  
Egbert Eggers ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Clinical Data ◽  
Clinical Characteristics ◽  
Regression Analyses ◽  
Health States ◽  
Tumor Registry ◽  
The Mean

Abstract Background The EQ-5D-5L questionnaire is used in oncology to generate health-related quality of life (HRQoL) weights and corresponding health states. The purpose was to explore the relationship between demographic and clinical characteristics and HRQoL among advanced or metastatic colorectal cancer (CRC) patients by linking clinical data of a German CRC registry to self-reported HRQoL measures from the EQ-5D-5L. Methods The study sample included patients with advanced or metastatic CRC currently recruited in the German Tumor Registry Colorectal Cancer. The EQ-5D-5L was administered once to patients who were at the start or at later stages of palliative treatment. Data on comorbidities, disease-specific health states, symptoms, and treatment status were drawn from the registry. Multivariate regression analyses were performed to explore the impact of patient and disease characteristics on HRQoL. Results In total, n = 433 questionnaires were included in the data analysis. Mean age of patients was 66.3 years and 61.2% were male. The mean EQ-5D-5L utility score was 0.82 and the mean EQ-5D-5L VAS score was 62.05. The regression analyses revealed that none of the demographic characteristics and few of the clinical characteristics, such as fatigue and pain, had a significant impact on the HRQoL. Conclusions The study demonstrated a reduced HRQoL of patients with advanced or metastatic CRC when compared to the general population. The symptoms fatigue and pain negatively affected the HRQoL, whereas other characteristics such as age, gender, and comorbidities did not have a significant impact on HRQoL.

Preoperative staging of colorectal cancer: accuracy of single portal venous phase multidetector computed tomography

2013 ◽  
Vol 37 (6) ◽  
pp. 1048-1053 ◽  
Author(s):  
Derya Tezcan ◽  
Aysel Türkvatan ◽  
Mehmet Akif Türkoğlu ◽  
Erdal Birol Bostancı ◽  
Zişan Sakaoğullları
Keyword(s):  
Colorectal Cancer ◽  
Computed Tomography ◽  
Multidetector Computed Tomography ◽  
Preoperative Staging ◽  
Portal Venous Phase ◽  
Venous Phase

scholarly journals Metronomic Low Dose Leucovorin- Fluorouracil versus Supportive Treatment for Patients with Recurrent or Metastatic Colorectal Cancer

2019 ◽  
pp. 1-8
Author(s):  
Hend M. Hamdey Rashed Elkalla ◽  
Mohamed Saad Elzahy ◽  
Shoukri Hassan Elazab
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Stable Disease ◽  
Low Dose ◽  
Palliative Chemotherapy ◽  
P Value ◽  
Supportive Treatment ◽  
Group A ◽  
The Mean ◽  
Group B

Introduction: There was an improvement in therapeutic regimens for advanced colorectal cancer (CRC) in the last few decades. The low dose metronomic palliative chemotherapy in patients with advanced CRC after the failure of standard chemotherapy led to a dramatic increase in efficacy, reduction of mortality rates, and improves survival in the form of control symptoms, and enhances or improves quality of life which is an important issue in that group of patients. Patients and Methods: We include 60 Patients with recurrent or metastatic colorectal cancer after failure of multiple lines of chemotherapy. The patients were randomized in two groups either to receive supportive treatment in group A (30 patients) or low dose weekly leucovorin 20 mg/m² plus 5-flourouracil 425 mg/m² for 3 weeks and 1 week rest in group B (30 patients). Patients in group B received palliative chemotherapy for 4 months at least. Results: After a follow up period of 19 months, the mean time to progression (TTP) is 4.9 months for the group (A) but is higher in group (B) as it is 7.8 months and it shows a statistically significant difference (P value <0.001). Also, the mean overall survival(OS) is 15.3 months for group (A) and 18.8 months for group (B) and this is statistically significant (P value <0.002). No grade 3 or 4 toxicity was detected. After 4 months of the study, 29 patients (96.6%) still have the stable disease compared to 18 patients (60%) of group (A). After 8 months, only 12 patients (40%) of group (B) show stable disease while all patients of group (A) have disease progression. Conclusion: We conclude that metronomic weekly leucovorin-5 FU could provide a good tolerable way to go on with chemotherapy treatment while at the same time not have major threatening side effects.

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