Journal of Clinical Medicine

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12 pages, 1116 KiB

Open AccessArticle

Development and Validation of an Early Mortality Risk Score for Older Patients Treated with Chemotherapy for Cancer

by Jaime Feliu, Alvaro Pinto, Laura Basterretxea, Borja López-San Vicente, Irene Paredero, Elisenda Llabrés, Beatriz Jiménez-Munárriz, Maite Antonio-Rebollo, Beatriz Losada, Enrique Espinosa, Regina Gironés, Ana Belén Custodio, María del Mar Muñoz, Mariana Díaz-Almirón, Jenifer Gómez-Mediavilla, María Dolores Torregrosa, Gema Soler, Patricia Cruz, Oliver Higuera, Juan Ignacio González-Montalvo and María José Molina-Garrido Show full author list Hide full author list

J. Clin. Med. 2021, 10(8), 1615; https://doi.org/10.3390/jcm10081615 - 10 Apr 2021

Cited by 8 | Viewed by 1708

Abstract

Background: Estimation of life expectancy in older patients is relevant to select the best treatment strategy. We aimed to develop and validate a score to predict early mortality in older patients with cancer. Patients and Methods: A total of 749 patients over 70 [...] Read more.

Background: Estimation of life expectancy in older patients is relevant to select the best treatment strategy. We aimed to develop and validate a score to predict early mortality in older patients with cancer. Patients and Methods: A total of 749 patients over 70 years starting new chemotherapy regimens were prospectively included. A prechemotherapy assessment that included sociodemographic variables, tumor/treatment variables, and geriatric assessment variables was performed. Association between these factors and early death was examined using multivariable logistic regression. Score points were assigned to each risk factor. External validation was performed on an independent cohort. Results: In the training cohort, the independent predictors of 6-month mortality were metastatic stage (OR 4.8, 95% CI [2.4–9.6]), ECOG-PS 2 (OR 2.3, 95% CI [1.1–5.2]), ADL ≤ 5 (OR 1.7, 95% CI [1.1–3.5]), serum albumin levels ≤ 3.5 g/dL (OR 3.4, 95% CI [1.7–6.6]), BMI < 23 kg/m² (OR 2.5, 95% CI [1.3–4.9]), and hemoglobin levels < 11 g/dL (OR 2.4, 95% CI (1.2–4.7)). With these results, we built a prognostic score. The area under the ROC curve was 0.78 (95% CI, 0.73 to 0.84), and in the validation set, it was 0.73 (95% CI: 0.67–0.79). Conclusions: This simple and highly accurate tool can help physicians making decisions in elderly patients with cancer who are planned to initiate chemotherapy treatment. Full article

(This article belongs to the Special Issue Current Status and Future Directions of Chemotherapy in Colorectal Cancer Therapy)

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6 pages, 1250 KiB

Open AccessArticle

Association between Primary Perioperative CEA Ratio, Tumor Site, and Overall Survival in Patients with Colorectal Cancer

by Thomas A. Odeny, Nicole Farha, Hannah Hildebrandand, Jessica Allen, Wilfred Vazquez, Maximillian Martinez, Ravi Kumar Paluri and Anup Kasi

J. Clin. Med. 2020, 9(12), 3848; https://doi.org/10.3390/jcm9123848 - 27 Nov 2020

Cited by 8 | Viewed by 1933

Abstract

There are differences in the incidence, clinical presentation, molecular pathogenesis, and outcome of colorectal cancer (CRC) based on tumor location. Emerging research suggests that the perioperative carcinoembryonic antigen (CEA) ratio (post-op/pre-op CEA) is a prognostic factor for CRC patients. We aimed to determine [...] Read more.

There are differences in the incidence, clinical presentation, molecular pathogenesis, and outcome of colorectal cancer (CRC) based on tumor location. Emerging research suggests that the perioperative carcinoembryonic antigen (CEA) ratio (post-op/pre-op CEA) is a prognostic factor for CRC patients. We aimed to determine the association between CEA ratio, tumor location, and overall survival (OS) among patients with CRC. We analyzed 427 patients who underwent resection for CRC at the University of Kansas Medical Center. After excluding those without pre- or post-operative CEA data, 207 patients were classified as either high (≥0.5) or low (<0.5) ratio. Primary outcomes were as follows: (1) OS stratified by CEA ratio; (2) OS stratified by tumor location; (3) OS stratified by tumor location among those with CEA elevation > 5 ng/mL at the time of recurrence. The Kaplan–Meier method was used to estimate survival rates. The median age was 62 years (inter-quartile range 51–71), 55% were male, 41% were smokers, 71% had left-sided tumors, the median pre-operative CEA was 3.1 ng/mL (inter-quartile range (IQR) 1.5–9.7), and 57% had a CEA ratio ≥0.5. The OS rates were 65.1% and 86.3% in patients with high versus low CEA ratios, respectively (log-rank p-value = 0.045). The OS rates were 64.4% and 77.3% in patients with right-sided vs. left-sided tumors, respectively (log-rank p-value = 0.5). Among patients with CEA levels greater than 5 at the time of recurrence, the OS rates were 42.9% and 43.4% in patients with right-sided vs. left-sided tumors, respectively (log-rank p-value = 0.7). There was a significantly higher survival among patients with low CEA ratios than among those with high CEA ratios. There was no difference in OS between left- versus right-sided tumors. Among patients with CEA elevation > 5 ng/mL at the time of recurrence, there was no difference in OS between left versus right-sided tumors. These findings warrant validation in a larger cohort as our sample size was limited. Full article

(This article belongs to the Special Issue Current Status and Future Directions of Chemotherapy in Colorectal Cancer Therapy)

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16 pages, 3054 KiB

Open AccessArticle

Impact of PD-L1 Scores and Changes on Clinical Outcome in Rectal Cancer Patients Undergoing Neoadjuvant Chemoradiotherapy

by Florian Huemer, Eckhard Klieser, Daniel Neureiter, Verena Schlintl, Gabriel Rinnerthaler, Franck Pagès, Amos Kirilovsky, Carine El Sissy, Wolfgang Iglseder, Franz Singhartinger, Tarkan Jäger, Adam Dinnewitzer, Nadja Zaborsky, Markus Steiner, Richard Greil and Lukas Weiss

J. Clin. Med. 2020, 9(9), 2775; https://doi.org/10.3390/jcm9092775 - 27 Aug 2020

Cited by 10 | Viewed by 2251

Abstract

Reports on the prognostic role of programmed death-ligand 1 (PD-L1) expression in rectal cancer are controversial. We investigated expression patterns and changes of PD-L1 in rectal cancer patients undergoing neoadjuvant chemoradiotherapy (CRT). Seventy-two patients diagnosed with rectal cancer and/or treated with fluorouracil-based neoadjuvant [...] Read more.

Reports on the prognostic role of programmed death-ligand 1 (PD-L1) expression in rectal cancer are controversial. We investigated expression patterns and changes of PD-L1 in rectal cancer patients undergoing neoadjuvant chemoradiotherapy (CRT). Seventy-two patients diagnosed with rectal cancer and/or treated with fluorouracil-based neoadjuvant CRT at the Department of Internal Medicine III of the Paracelsus Medical University Salzburg (Austria) between January 2003 and October 2012 were included. PD-L1 scoring was performed according to the tumor proportion score (TPS), combined positive score (CPS), and immune cell score (IC). PD-L1 TPS prior to neoadjuvant CRT had a statistically significant impact on survival (median: ≤1%: 95.4 months (95% CI: 51.8—not reached) vs. >1%: not reached, p = 0.03, log-rank). Patients with a PD-L1 TPS ≤1% prior to and after CRT showed an inferior survival compared to all other patients (median: 56.7 months (95% CI: 51.4—not reached) vs. not reached, p = 0.005, log-rank). In multivariate analysis, PD-L1 TPS prior to neoadjuvant CRT (>1% vs. ≤1%, hazard ratio: 0.29 (95% CI: 0.11–0.76), p = 0.01) remained independently associated with survival. In conclusion, low PD-L1 TPS was associated with inferior survival in rectal cancer patients undergoing neoadjuvant CRT. A prospective validation of the prognostic value of PD-L1 expression in rectal cancer patients within a clinical trial is necessitated. Full article

(This article belongs to the Special Issue Current Status and Future Directions of Chemotherapy in Colorectal Cancer Therapy)

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Review

Jump to: Research

14 pages, 696 KiB

Open AccessReview

Are Quality of Randomized Clinical Trials and ESMO-Magnitude of Clinical Benefit Scale Two Sides of the Same Coin, to Grade Recommendations for Drug Approval?

by Adela Rodriguez, Francis Esposito, Helena Oliveres, Ferran Torres and Joan Maurel

J. Clin. Med. 2021, 10(4), 746; https://doi.org/10.3390/jcm10040746 - 13 Feb 2021

Cited by 1 | Viewed by 1772

Abstract

The approval of a new drug for cancer treatment by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) is based on positive, well-designed randomized phase III clinical trials (RCTs). However, not all of them are analyzed to support [...] Read more.

The approval of a new drug for cancer treatment by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) is based on positive, well-designed randomized phase III clinical trials (RCTs). However, not all of them are analyzed to support the recommendations. For this reason, there are different scales to quantify and evaluate the quality of RCTs and the magnitude of the clinical benefits of new drugs for treating solid tumors. In this review, we discuss the value of the progression-free survival (PFS) as an endpoint in RCTs and the concordance between it and the overall survival (OS) as a measure of the quality of clinical trial designs. We summarize and analyze the different scales to evaluate the clinical benefits of new drugs such as the The American Society of Clinical Oncology value framework (ASCO-VF-NHB16) and European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) and the concordance between them, focusing on metastatic colorectal cancer (mCRC). We propose several definitions that would help to evaluate the quality of RCT, the magnitude of clinical benefit and the appropriate approval of new drugs in oncology. Full article

(This article belongs to the Special Issue Current Status and Future Directions of Chemotherapy in Colorectal Cancer Therapy)

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13 pages, 254 KiB

Open AccessReview

First-Line Maintenance Treatment in Metastatic Colorectal Cancer (mCRC): Quality and Clinical Benefit Overview

by Marta Martín-Richard and Maria Tobeña

J. Clin. Med. 2021, 10(3), 470; https://doi.org/10.3390/jcm10030470 - 26 Jan 2021

Cited by 3 | Viewed by 1685

Abstract

Different strategies of maintenance therapy (sequential CT, intermittent CT, intermittent CT and MAbs, or de-escalation MAbs monotherapy) after first-line treatment are undertaken. Many randomized clinical trials (RCT), which evaluated these approaches, suffer from incorrect design, heterogenous primary endpoints, inadequate size, and other methodology [...] Read more.

Different strategies of maintenance therapy (sequential CT, intermittent CT, intermittent CT and MAbs, or de-escalation MAbs monotherapy) after first-line treatment are undertaken. Many randomized clinical trials (RCT), which evaluated these approaches, suffer from incorrect design, heterogenous primary endpoints, inadequate size, and other methodology flaws. Drawing any conclusions becomes challenging and recommendations are mainly vague. We evaluated those studies from another perspective, focusing on the design quality and the clinical benefit measure with a more objective and accurate methodology. These data allowed a clearer and more exact overview of the statement in maintenance treatment. Full article

(This article belongs to the Special Issue Current Status and Future Directions of Chemotherapy in Colorectal Cancer Therapy)

16 pages, 311 KiB

Open AccessReview

Chemotherapy and Targeted Agents in the Treatment of Elderly Patients with Metastatic Colorectal Cancer

by Albert Tuca, Rosa Gallego, Ismael Ghanem, Mireia Gil-Raga and Jaime Feliu

J. Clin. Med. 2020, 9(12), 4015; https://doi.org/10.3390/jcm9124015 - 11 Dec 2020

Cited by 8 | Viewed by 2191

Abstract

Colorectal cancer (CRC) is one of the main causes of cancer death in the elderly. The older patients constitute a heterogeneous group in terms of functional status, comorbidities, and aging-related conditions. Therefore, therapeutic decisions need to be individualized. Additionally, a higher toxicity risk [...] Read more.

Colorectal cancer (CRC) is one of the main causes of cancer death in the elderly. The older patients constitute a heterogeneous group in terms of functional status, comorbidities, and aging-related conditions. Therefore, therapeutic decisions need to be individualized. Additionally, a higher toxicity risk comes from the fact that pharmacokinetics and pharmacodynamics of the drugs as well as the tissue tolerance can be altered with aging. Although the chemotherapy efficacy in metastatic colorectal cancer (mCRC) is similar for older and young patients, more toxicity is presented in the elderly. While the mono-chemotherapy provides the same benefit for young and older patients, doublets front-line chemotherapy improves progression-free survival (PFS) but not overall survival (OS) in the elderly. Furthermore, the benefit of the addition of bevacizumab to chemotherapy in older patients has been shown in several clinical trials, while the clinical data for the benefit of anti-epidermal growth factor antibodies are scarcer. Immunocheckpoint inhibitors could be an appropriate option for patients with microsatellite instability (MSI) tumors. A prior geriatric assessment is required before deciding the type of treatment in order to offer the best therapeutic option. Full article

(This article belongs to the Special Issue Current Status and Future Directions of Chemotherapy in Colorectal Cancer Therapy)

10 pages, 219 KiB

Open AccessReview

Metastatic Colorectal Cancer. First Line Therapy for Unresectable Disease

by Jorge Aparicio, Francis Esposito, Sara Serrano, Esther Falco, Pilar Escudero, Ana Ruiz-Casado, Hermini Manzano and Ana Fernandez-Montes

J. Clin. Med. 2020, 9(12), 3889; https://doi.org/10.3390/jcm9123889 - 30 Nov 2020

Cited by 32 | Viewed by 3162

Abstract

Colorectal cancer (CRC) is a commonly diagnosed malignancy. The prognosis of patients with unresectable, metastatic colorectal cancer (mCRC) is dismal and medical treatment is mainly palliative in nature. Although chemotherapy remains the backbone of treatment, the landscape is changing with the understanding of [...] Read more.

Colorectal cancer (CRC) is a commonly diagnosed malignancy. The prognosis of patients with unresectable, metastatic colorectal cancer (mCRC) is dismal and medical treatment is mainly palliative in nature. Although chemotherapy remains the backbone of treatment, the landscape is changing with the understanding of its heterogeneity and molecular biology. First-line therapy relies on a combination of chemotherapy and targeted therapies, according to clinical patient characteristics and tumor molecular profile. Here we review current evidence from randomized clinical trials for using chemotherapy doublets or triplets, and for the addition of bevacizumab or anti-epidermal growth factor receptor (EGFR) agents. Novel therapies developed for small, selected populations are also discussed. Full article

(This article belongs to the Special Issue Current Status and Future Directions of Chemotherapy in Colorectal Cancer Therapy)

14 pages, 452 KiB

Open AccessReview

Current Treatments of Metastatic Colorectal Cancer with Immune Checkpoint Inhibitors—2020 Update

by Gerhard Jung, Daniel Benítez-Ribas, Ariadna Sánchez and Francesc Balaguer

J. Clin. Med. 2020, 9(11), 3520; https://doi.org/10.3390/jcm9113520 - 31 Oct 2020

Cited by 19 | Viewed by 3793

Abstract

During the last 20 years, chemotherapy has improved survival rates of colorectal cancer (CRC). However, the majority of metastatic cases do not respond to or progress after first line conventional chemotherapy and contribute to the fatalities of patients with CRC. Insights into the [...] Read more.

During the last 20 years, chemotherapy has improved survival rates of colorectal cancer (CRC). However, the majority of metastatic cases do not respond to or progress after first line conventional chemotherapy and contribute to the fatalities of patients with CRC. Insights into the immune contexture of the tumor microenvironment (TME) have enabled the development of new systemic treatments that boost the host immune system against the tumor—the immune checkpoint inhibitors (ICI). These promising drugs have already shown astonishing efficacies in other cancer types and have raised new hope for the treatment of metastatic CRC (mCRC). In this review, we will summarize the results of the clinical trials that led to their accelerated approval by the U.S. Food and Drug Administration (FDA) in 2017, as well as all relevant recent studies conducted since then—some of which are not published yet. We will focus on therapeutic efficacy, but also discuss the available data for drug safety and security, changes in quality of life indicators and predictive biomarkers for treatment response. The burgeoning evidence for a potential use of ICIs in other settings than mCRC will also be mentioned. For each trial, we have made a preliminary assessment of the quality of clinical trial design and of the “European Society of Medical Oncology (ESMO) magnitude of clinical benefit” (ESMO-MCBS) in order to provide the first evidence-based recommendation to the reader. Full article

(This article belongs to the Special Issue Current Status and Future Directions of Chemotherapy in Colorectal Cancer Therapy)

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33 pages, 2073 KiB

Open AccessReview

A Review of GC-Based Analysis of Non-Invasive Biomarkers of Colorectal Cancer and Related Pathways

by Fernanda Monedeiro, Maciej Monedeiro-Milanowski, Tomasz Ligor and Bogusław Buszewski

J. Clin. Med. 2020, 9(10), 3191; https://doi.org/10.3390/jcm9103191 - 01 Oct 2020

Cited by 14 | Viewed by 2862

Abstract

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the world. In Europe, it is the second most common cause of cancer-related deaths. With the advent of metabolomics approaches, studies regarding the investigation of metabolite profiles related to CRC have been [...] Read more.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the world. In Europe, it is the second most common cause of cancer-related deaths. With the advent of metabolomics approaches, studies regarding the investigation of metabolite profiles related to CRC have been conducted, aiming to serve as a tool for early diagnosis. In order to provide further information about the current status of this field of research, 21 studies were systematically reviewed, regarding their main findings and analytical aspects. A special focus was given to the employment of matrices obtained non-invasively and the use of gas chromatography as the analytical platform. The relationship between the reported volatile and non-volatile biomarkers and CRC-related metabolic alterations was also explored, demonstrating that many of these metabolites are connected with biochemical pathways proven to be involved in carcinogenesis. The most commonly reported CRC indicators were hydrocarbons, aldehydes, amino acids and short-chain fatty acids. These potential biomarkers can be associated with both human and bacterial pathways and the analysis based on such species has the potential to be applied in the clinical practice as a low-cost screening method. Full article

(This article belongs to the Special Issue Current Status and Future Directions of Chemotherapy in Colorectal Cancer Therapy)

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