Factors associated with Trifluridine/Tipiracil (TAS-102) effectiveness in patients with refractory metastatic colorectal cancer: real-life data from the Czech Republic.

Abstract Background: Trifluridine/tipiracil (TAS-102) is effective in refractory metastatic colorectal cancer (mCRC). Currently, no predictive biomarkers are established and used in clinical practice. Methods: We analyzed data of 160 patients treated with TAS-102 in real clinical practice in the Czech Republic. Different factors associated with progression-free survival (PFS) and overall survival (OS) were evaluated. Results: Median PFS was 3.3 months, and median OS 10.2 months. Factors significantly associated with PFS and/or OS were: ECOG performance status (PS), time from diagnosis of mCRC > 24 months, initiation of treatment > 3 months from last fluoropyrimidine, number of metastatic sites, baseline CRP level, WBC count, neutrophils count, monocytes count, neutrophil to lymphocyte ratio, development of neutropenia, thrombocytopenia, diarrhea, required dose reduction and cycle delay. We developed a scoring system TAScore from factors available at the beginning of treatment. One point each was assigned to the following factors (PS, diagnosis of mCRC > 24 months, initiation of TAS-102 > 3 months from fluoropyrimidine, baseline CRP, WBC, monocytes count < 0.5 × 10 9 /L) and patients were divided into 3 groups: high risk group (0 to 1 point), intermediate (2 to 3), favorable with 4 or more points. OS according to risk group was: 5.7 months for high risk, 8.7 for intermediate, 12.8 for favorable (P < 0.001). TAScore was also associated with PFS (P < 0.001). Conclusions : TAS-102 is effective in patients with refractory mCRC. We propose simple scoring system TAScore to help with precise patient selection at the beginning of TAS-102 treatment.

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Prediction of trifluridine/tipiracil (TAS-102) effectiveness in patients with refractory metastatic colorectal cancer (mCRC): Real-life data from the Czech Republic.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e15102 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e15102-e15102

Author(s):

Peter Grell ◽

Josef Dvorak ◽

Michal Vocka ◽

Stanislav John ◽

Helena Tuskova ◽

...

Keyword(s):

Czech Republic ◽

Clinical Practice ◽

High Risk ◽

Scoring System ◽

Risk Group ◽

Real Life ◽

Predictive Biomarkers ◽

Progression Free Survival ◽

Median Number ◽

High Risk Group

e15102 Background: TAS-102 is effective in refractory mCRC and significantly improved survival versus placebo. Currently no predictive biomarkers are established and used in clinical practice. Methods: We analyzed data of 160 patients treated with TAS-102 in real clinical practice in Czech Republic. Different factors associated with progression-free survival (PFS) and overall survival (OS) were evaluated. Results: Baseline patients’ characteristics: median age 66 years (range 28-83), 106 patients were male (66.3 %), ECOG PS 0 had 38.1 %, RAS wt 45 %. Anti-VEGF treatment had 83.1 %, anti-EGFR 43.8 %. Median number of TAS-102 treatment line was 3 (range, 2 – 8), median TAS-102 cycles 3 (range 1 – 27). At the time of analysis 15 % continued in treatment, 73.7 % discontinued due to progression, 6.9 % due to toxicity, 3.8 % decided to discontinue in treatment. Median PFS was 3.3 months (95% CI, 3.0 – 3.5), and median OS 10.2 months (95% CI, 8.9 – 11.8). Factors significantly associated with PFS and/or OS were: PS, time from diagnosis of mCRC, initiation of TAS-102 treatment > 3 months from last fluoropyrimidine, baseline CRP, WBC, neutrophils count, monocytes count, NLR, neutropenia ≥ G2, diarrhea ≥ G1, thrombocytopenia ≥ G2, required TAS-102 dose reduction and cycle delay. We developed a scoring system TAScore from factors at the beginning of treatment (PS 0, initiation of TAS-102 > 3 months from fluoropyrimidine, time from diagnosis of mCRC, baseline CRP, WBC, monocytes count < 0.5 × 109/L). For each factor patient received 1 point, the overall score was the sum of these points and patients were divided into 3 groups: high risk group with 0 to 1 point, intermediate with 2 to 3, favorable with 4 or more points. OS according to risk group was: 5.7 months for high risk (11 patients), 8.7 for intermediate (63), 12.8 for favorable (59) (P < 0.0001). TAScore was also associated with PFS: 2.4 months for high risk, 2.9 intermediate and 3.9 for favorable risk group (P < 0.0001). Conclusions: TAS-102 is effective in patients with refractory mCRC. We propose simple scoring system TAScore to help with precise patient selection at the beginning of TAS-102 treatment.

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Stage IV Colorectal Cancer Patients with High Risk Mutation Profiles Survived 16 Months Longer with Individualized Therapies

Cancers ◽

10.3390/cancers12020393 ◽

2020 ◽

Vol 12 (2) ◽

pp. 393

Author(s):

Alexander Hendricks ◽

Anu Amallraja ◽

Tobias Meißner ◽

Peter Forster ◽

Philip Rosenstiel ◽

...

Keyword(s):

Colorectal Cancer ◽

Clinical Practice ◽

High Risk ◽

Metastatic Colorectal Cancer ◽

Cancer Patients ◽

Standard Of Care ◽

High Risk Patients ◽

Risk Patients ◽

Individualized Treatments ◽

Colorectal Cancer Patients

Personalized treatment vs. standard of care is much debated, especially in clinical practice. Here we investigated whether overall survival differences in metastatic colorectal cancer patients are explained by tumor mutation profiles or by treatment differences in real clinical practice. Our retrospective study of metastatic colorectal cancer patients of confirmed European ancestry comprised 54 Americans and 54 gender-matched Germans. The Americans received standard of care, and on treatment failure, 35 patients received individualized treatments. The German patients received standard of care only. Tumor mutations, tumor mutation burden and microsatellite status were identified by using the FoundationOne assay or the IDT Pan-Cancer assay. High-risk patients were identified according to the mutational classification by Schell and colleagues. Results: Kaplan–Meier estimates show the high-risk patients to survive 16 months longer under individualized treatments than those under only standard of care, in the median (p < 0.001). Tumor mutation profiles stratify patients by risk groups but not by country. Conclusions: High-risk patients appear to survive significantly longer (p < 0.001) if they receive individualized treatments after the exhaustion of standard of care treatments. Secondly, the tumor mutation landscape in Americans and Germans is congruent and thus warrants the transatlantic exchange of successful treatment protocols and the harmonization of guidelines.

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Efficacy, Safety and Cost of Regorafenib in Patients with Metastatic Colorectal Cancer in French Clinical Practice

Clinical Medicine Insights Oncology ◽

10.4137/cmo.s38335 ◽

2016 ◽

Vol 10 ◽

pp. CMO.S38335 ◽

Cited By ~ 12

Author(s):

Fabien Calcagno ◽

Sabrina Lenoble ◽

Zaher Lakkis ◽

Thierry Nguyen ◽

Samuel Limat ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Clinical Practice ◽

Adverse Events ◽

Metastatic Colorectal Cancer ◽

Real Life ◽

Outpatient Setting ◽

Toxic Effects ◽

Duration Of Treatment ◽

Heavily Pretreated

Background Regorafenib is an orally administered multikinase inhibitor that has been approved for patients with chemotherapy-refractory metastatic colorectal cancer (mCRC). Even though regorafenib significantly improved survival in two international phase 3 trials (CORRECT and CONCUR), a high rate of treatment-related toxic effects and dose modifications were observed with a modest benefit. The aim of this study was to provide information concerning the efficacy, safety, and cost of regorafenib in patients with mCRC in clinical practice. Material and Methods We retrospectively reviewed patients treated with regorafenib monotherapy for unresectable mCRC in five Franche-Comté cancer hospitals (France). The primary end point was overall survival. Secondary end points were safety and descriptive cost analyses of patients treated with regorafenib in clinical practice. Another aim of this study was to assess the impact of regorafenib prescription on the risk of hospitalization in real-life practice. Results From January 2014 to August 2014, 29 consecutive patients were enrolled. Patients were heavily pretreated and were refractory to standard chemotherapies. The primary tumor sites were the colon and the rectum for 55% and 45% of patients, respectively. Fifteen patients (51%) harbored an RAS mutation. Eastern Cooperative Oncology Group - Performance Status (PS) was 0–1 for 86% of patients and 2 for 14% of patients. Nineteen patients (66%) initially received reduced doses of 120 or 80 mg/day. The median duration of treatment was 2.5 months (range, 0.13–11.4 months). Treatment-related adverse events occurred in 86% of patients. The most frequent adverse events of any grade were fatigue (35%), diarrhea (20%), and hand-foot skin reaction (20%). Grade 3 or 4 treatment-related adverse events occurred in 10 patients (35%). Three patients (10%) were admitted to hospital due to drug-related severe adverse events. The mean cost of patient management with regorafenib for the duration of treatment was 9908 ± 8191€, and median cost was 7917€ (Interquartile range (IQR) 4469-13,042). The median overall survival was six months (95% confidence interval, five to eight months). Conclusions The safety and efficacy of regorafenib in heavily pretreated mCRC patients was comparable, in our study, to prospective and retrospective trials. Toxic effects were mostly manageable in an outpatient setting. Regorafenib itself represented the most important (93%) part of supported costs. Even though most side effects were manageable in an outpatient setting, severe adverse events occurred from hospitalization in 10% of patients. These data should be confirmed in a larger real-life-based cohort. Identification of predictive biomarkers is needed for mCRC patient selection for regorafenib treatment.

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Prognostic utility of neutrophil-to-lymphocyte ratio in patients with metastatic colorectal cancer treated using different modalities

Current Oncology ◽

10.3747/co.27.6573 ◽

2020 ◽

Vol 27 (5) ◽

Author(s):

G. Nogueira-Costa ◽

I. Fernandes ◽

R. Gameiro ◽

J. Gramaça ◽

A.T. Xavier ◽

...

Keyword(s):

Colorectal Cancer ◽

High Risk ◽

Metastatic Colorectal Cancer ◽

Real World ◽

Cox Regression ◽

Risk Group ◽

High Risk Group ◽

Low Risk ◽

First Line ◽

Kaplan Meier

Introduction Inflammation is a critical component in carcinogenesis. The neutrophil-to-lymphocyte ratio (nlr) has been retrospectively studied as a biomarker of prognosis in metastatic colorectal cancer (mcrc). Compared with a low nlr, a high nlr is associated with worse prognosis. In the present study, we compared real-world survival for patients with mcrc based on their nlr group, and we assessed the utility of the nlr in determining first-line chemotherapy and metastasectomy benefit. Methods In this retrospective and descriptive analysis of patients with mcrc undergoing first-line chemotherapy in a single centre, the last systemic absolute neutrophil and lymphocyte count before treatment was used for the nlr. A receiver operating characteristic curve was used to estimate the nlr cut-off value, dividing the patients into low and high nlr groups. Median overall survival (mos) was compared using Kaplan–Meier curves and the log-rank test. A multivariate analysis was performed using a Cox regression model. Results The 102 analyzed patients had a median follow-up of 15 months. Regardless of systemic therapy, approximately 20% of patients underwent metastasectomy. The nlr cut-off was established at 2.35, placing 45 patients in the low-risk group (nlr < 2.35) and 57 in the high-risk group (nlr ≥ 2.35). The Kaplan–Meier analysis showed a mos of 39.1 months in the low-risk group and 14.4 months in the high-risk group (p < 0.001). Multivariate Cox regression on the nlr estimated a hazard ratio of 3.08 (p = 0.01). Survival analysis in each risk subgroup, considering the history of metastasectomy, was also performed. In the low-risk group, mos was longer for patients undergoing metastasectomy than for those not undergoing the procedure (95.2 months vs. 22.6 months, p = 0.05). In the high-risk group, mos was not statistically different for patients undergoing or not undergoing metastasectomy (24.3 months vs. 12.7 months, p = 0.08). Conclusions Our real-world data analysis of nlr in patients with mcrc confirmed that this biomarker is useful in predicting survival. It also suggests that nlr is an effective tool to choose first-line treatment and to predict the benefit of metastasectomy.

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Use of epidemiological analyses in development of colorectal cancer clinical practice guidelines in the Czech Republic

International Journal of Evidence-Based Healthcare ◽

10.1097/xeb.0000000000000187 ◽

2019 ◽

Vol 17 ◽

pp. S57-S61 ◽

Cited By ~ 1

Author(s):

Jitka Klugarová ◽

Miloslav Klugar ◽

Jan Mužík ◽

Jiří Jarkovský ◽

Radim Líčeník ◽

...

Keyword(s):

Colorectal Cancer ◽

Czech Republic ◽

Clinical Practice ◽

Clinical Practice Guidelines ◽

Practice Guidelines ◽

The Czech Republic

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Intensive multidisciplinary treatment strategies and patient resilience to challenge long-term survival in metastatic colorectal cancer: a case report in real life and clinical practice

Annals of Translational Medicine ◽

10.21037/atm-20-6636 ◽

2021 ◽

Vol 0 (0) ◽

pp. 0-0

Author(s):

Gemma Bruera ◽

◽

Francesco Pepe ◽

Umberto Malapelle ◽

Mario Di Staso ◽

...

Keyword(s):

Colorectal Cancer ◽

Case Report ◽

Clinical Practice ◽

Metastatic Colorectal Cancer ◽

Multidisciplinary Treatment ◽

Real Life ◽

Treatment Strategies ◽

Term Survival ◽

Long Term Survival

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On Geropsychology in the Czech Republic

GeroPsych ◽

10.1024/1662-9647/a000066 ◽

2012 ◽

Vol 25 (3) ◽

pp. 161-166

Author(s):

Hana Stepankova ◽

Eva Jarolimova ◽

Eva Dragomirecka ◽

Irena Sobotkova ◽

Lenka Sulova ◽

...

Keyword(s):

Czech Republic ◽

Clinical Practice ◽

Old Age ◽

Cognitive Rehabilitation ◽

The Czech Republic ◽

Rehabilitation Research

This work provides an overview of psychology of aging and old age in the Czech Republic. Historical roots as well as recent activities are listed including clinical practice, cognitive rehabilitation, research, and the teaching of geropsychology.

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