Monitoring Of Cancer Patients Research Articles

The clinical and translational research activities at the INT \u2013 IRCCS \u201cFondazione Pascale\u201d cancer center (Naples, Italy) during the COVID-19 pandemic

COVID-19 pandemic following the outbreak in China and Western Europe, where it finally lost the momentum, is now devastating North and South America. It has not been identified the reason and the molecular mechanisms of the two different patterns of the pulmonary host responses to the virus from a minimal disease in young subjects to a severe distress syndrome (ARDS) in older subjects, particularly those with previous chronic diseases (including diabetes) and cancer. The Management of the Istituto Nazionale Tumori - IRCCS “Fondazione Pascale” in Naples (INT-Pascale), along with all Health professionals decided not to interrupt the treatment of those hospitalized and to continue, even if after a careful triage in order not to allow SARS-CoV-2 positive subjects to access, to take care of cancer patients with serious conditions. Although very few (n = 3) patients developed a symptomatic COVID-19 and required the transfer to a COVID-19 area of the Institute, no patients died during the hospitalization and completed their oncology treatment. Besides monitoring of the patients, all employees of the Institute (physicians, nurses, researchers, lawyers, accountants, gatekeepers, guardians, janitors) have been tested for a possible exposure. Personnel identified as positive, has been promptly subjected to home quarantine and subdued to health surveillance. One severe case of respiratory distress has been reported in a positive employees and one death of a family member. Further steps to home monitoring of COVID-19 clinical course have been taken with the development of remote Wi-Fi connected digital devices for the detection of early signs of respiratory distress, including heart rate and oxygen saturation.In conclusion cancer care has been performed and continued safely also during COVID-19 pandemic and further remote home strategies are in progress to ensure the appropriate monitoring of cancer patients.

CA 19.9 na Coledocolitíase: Caso Clínico

Com base num paciente com elevação acentuada dos níveis de CA 19.9 sérico, portador de coledocolitíase, são feitas algumas considerações sobre a utilidade dos marcadores tumorais na prática clínica.Um nível elevado deste antigénio nem sempre corresponde a patologia maligna, não sendo específico da mesma, retirando importância diagnóstica ao mesmo, muitas vezes, confundindo situações. Estudos retrospetivos demonstram que o uso indevido dos marcadores tumorais encarece os sistemas de saúde, deturpam e atrasam diagnósticos. No entanto, os autores reforçam o seu papel no acompanhamento de pacientes oncológicos, com diagnóstico comprovado de neoplasias, podendo ser benéficos para decisões terapêuticas futuras e vigilância clínica.

Telemetric electrocardiography in diagnostics of cardiotoxic heart rhythm disorders and conductivity in oncologic patients

Aim.Assessment of the possibility to use ECG-telemetry in order to increase the efficiency of cardiotoxic effect diagnosis in cancer patients with chemotherapy.
 Material and methods.Remote dynamic monitoring for 6 months was carried out in 31 cardio-oncological patients (in 17 prostate cancer (PC), in 14 breast cancer (BC), mean age was 53.6 (50.1; 56.8) years and 48.3 (38.8; 57.1) years, respectively; FC NYHA IIII; left ventricular ejection fraction 47.4% (40.2; 57.3) and 43.2% (39.7; 58.9), respectively; Mini-Mental State Examination from 30 to 24 points 27.6 (25.4; 29,1) and 28.2 (25.1; 28.8), respectively. ECG-telemetry was performed according to the principle of auto-translation using individual ECG recorders, mobile devices and the ECG Dongle Internet application (Nordavind-Dubna, Russia). Storage, analysis of information and telemedicine consultation was perfomed with the CardioСloud asynchronous tele-cardiological platform. ECG was registered with a frequency of at least 5 times/day and additionally repeatedly in the presence of symptoms and patient desires, duration 1020 minutes.
 Results.Previously undocumented ECG changes were remotely recorded in patients for 6 months of follow-up: in 87.0% of patients sinus tachycardia, against which ventricular extrasystole of various gradations (32.3%), supraventricular extrasystole (22.6%), transient tachy-dependent blockade of the bundle of His legs were recorded (9.7%). In 64.7% of PC patients and in 42.8% of BC patients rhythm disturbances were detected in combination with depression of theSTsegment. Paroxysms of atrial fibrillation were reported in 17.6% of PC patients and in 14.3% BC patients. In 35.5% of patients the detected ECG changes were asymptomatic.
 Conclusion.Remote dynamic monitoring in cancer patients receiving chemotherapy involving ECG recording scheme (5 times/day, 1020 min) with ECG telemetry is an effective and unexpensive method for detecting ECG changes in the phenomenon of cardiotoxicity.

1780TiP Ambulatory follow-up care and monitoring of cancer patients during SARS-CoV-2 pandemic by collecting blood samples at home and monitoring systemic therapy using a smartphone application (COREO-trial)

There is a broad range of clinical presentations of a SARS-CoV-2 viral infection varying from asymptomatic, sensation of a mild cold or flu to severe bilateral pneumonia and death. Liang et al. already reported the most severe complications in cancer patients particularly when they had undergone chemotherapy or surgery over the last month. In absence of a vaccine or adequate treatment of COVID-19 current measures to minimize the infectious risk of SARS-CoV-2 in a cancer patient population are focused on social distancing and protective measures for the medical and nursing staff members, and in some settings also patients.

OMIP-069: Forty-Color Full Spectrum Flow Cytometry Panel for Deep Immunophenotyping of Major Cell Subsets in Human Peripheral Blood.

PURPOSE AND APPROPRIATE SAMPLE TYPESThis 40‐color flow cytometry‐based panel was developed for in‐depth immunophenotyping of the major cell subsets present in human peripheral blood. Sample availability can often be limited, especially in cases of clinical trial material, when multiple types of testing are required from a single sample or timepoint. Maximizing the amount of information that can be obtained from a single sample not only provides more in‐depth characterization of the immune system but also serves to address the issue of limited sample availability. The panel presented here identifies CD4 T cells, CD8 T cells, regulatory T cells, γδ T cells, NKT‐like cells, B cells, NK cells, monocytes and dendritic cells. For each specific cell type, the panel includes markers for further characterization by including a selection of activation and differentiation markers, as well as chemokine receptors. Moreover, the combination of multiple markers in one tube might lead to the discovery of new immune phenotypes and their relevance in certain diseases. Of note, this panel was designed to include only surface markers to avoid the need for fixation and permeabilization steps. The panel can be used for studies aimed at characterizing the immune response in the context of infectious or autoimmune diseases, monitoring cancer patients on immuno‐ or chemotherapy, and discovery of unique and targetable biomarkers. Different from all previously published OMIPs, this panel was developed using a full spectrum flow cytometer, a technology that has allowed the effective use of 40 fluorescent markers in a single panel. The panel was developed using cryopreserved human peripheral blood mononuclear cells (PBMC) from healthy adults (Table 1). Although we have not tested the panel on fresh PBMCs or whole blood, it is anticipated that the panel could be used in those sample preparations without further optimization. @ 2020 Cytek Biosciences, Inc. Cytometry Part A published by Wiley Periodicals LLC on behalf of International Society for Advancement of Cytometry.

Combined C-Reactive Protein and Novel Inflammatory Parameters as a Predictor in Cancer-What Can We Learn from the Hematological Experience?

The acute phase reaction is a systemic response to acute or chronic inflammation. The serum level of C-reactive protein (CRP) is the only acute phase biomarker widely used in routine clinical practice, including its uses for prognostics and therapy monitoring in cancer patients. Although Interleukin 6 (IL6) is a main trigger of the acute phase reactions, a series of acute phase reactants can contribute (e.g., other members in IL6 family or IL1 subfamily, and tumor necrosis factor α). However, the experience from patients receiving intensive chemotherapy for hematological malignancies has shown that, besides CRP, other biomarkers (e.g., cytokines, soluble cytokine receptors, soluble adhesion molecules) also have altered systemic levels as a part of the acute phase reaction in these immunocompromised patients. Furthermore, CRP and white blood cell counts can serve as a dual prognostic predictor in solid tumors and hematological malignancies. Recent studies also suggest that biomarker profiles as well as alternative inflammatory mediators should be further developed to optimize the predictive utility in cancer patients. Finally, the experience from allogeneic stem cell transplantation suggests that selected acute phase reactants together with specific markers of organ damages are useful for predicting or diagnosing graft versus host disease. Acute phase proteins may also be useful to identify patients (at risk of) developing severe immune-mediated toxicity after anticancer immunotherapy. To conclude, future studies of acute phase predictors in human malignancies should not only investigate the conventional inflammatory mediators (e.g., CRP, white blood cell counts) but also combinations of novel inflammatory parameters with specific markers of organ damages.

Risk of QTc prolongation among cancer patients treated with tyrosine kinase inhibitors.

QTc interval prolongation can lead to life-threatening complications such as Torsade de Pointes (TdP), ventricular tachycardia (VT) and sudden cardiac death (SCD). It can occur with tyrosine kinase inhibitors (TKIs) but comparative real-world analyses on the incidence and complication rates are scarce. We retrospectively reviewed all cancer patients treated with TKI therapy at Mayo Clinic between January 2005 and December 2018 and had at least two ECGs (before and after TKI). For each TKI type, we determined the administration rate and incidence of QTc prolongation. QTc prolongation was defined as a corrected QT interval (by Fridericia formula) ≥450 ms in men and ≥470 ms in women. A total of 618 cancer patients were included with 902 TKI administrations, of which 654 (72.5%) were accounted for by pazopanib, sunitinib, imatinib, nilotinib and dasatinib. QTc prolongation (any grade) was reported in 28.8%, most commonly with nilotinib (38.7%) and dasatinib (41.7%). A QTc interval ≥500 ms and a QTc increase ≥60 ms was documented in 46 and 63 administrations, respectively. Life-threatening toxicity was seen in 14 cases (5.4% of QTc prolongation cases) including VT in 9, SCD in 3 and TdP in two administrations. The response to QTc prolongation was: discontinuation in 68%, dose reduction in 13.5%, temporary hold in 8.1% and no action in 10.4%. In conclusion, QTc prolongation with TKI therapy is very common (∼1/3 of cases) and in 5% (1.7% overall) associated with life-threatening complications. These data support recommendations for careful ECG monitoring in cancer patients undergoing TKI therapy.

Close2U: An App for Monitoring Cancer Patients with Enriched Information from Interaction Patterns

The management of cancer patients' symptoms in doctor consultations is a cornerstone in clinical care, this process being fundamental for the follow-up of the evolution of these. This article presents an application that allows collecting periodically and systematically the data of cancer patients and their visualization by the medical team. In this article, we made the analysis, design, implementation, and final evaluation by analyzing the correlation of this data collection with interaction patterns to determine how the user information can be enriched with information from the interaction patterns. We have followed an agile methodology based on the iterative and incremental development of successive prototypes with increased fidelity, where the requirements and solutions have evolved over time according to the need and assessments made. The comprehensive analysis of the patient's condition allowed us to perform a first analysis of the correlation of the states of patients concerning mood, sleeping quality, and pain with the interaction patterns. A future goal of this project is to optimize the process of data collection and the analysis of information. Another future goal is to reduce the time dedicated to reporting the evolution of symptoms in face-to-face consultations and to help professionals in analyzing the patient's evolution even in the period that has not been attended in person.

Monitoring Response to Home Parenteral Nutrition in Adult Cancer Patients.

Current guidelines recommend home parenteral nutrition (HPN) for cancer patients with chronic deficiencies of dietary intake or absorption when enteral nutrition is not adequate or feasible in suitable patients. HPN has been shown to slow down progressive weight loss and improve nutritional status, but limited information is available on the monitoring practice of cancer patients on HPN. Clinical management of these patients based only on nutritional status is incomplete. Moreover, some commonly used clinical parameters to monitor patients (weight loss, body weight, body mass index, and oral food intake) do not accurately reflect patient’s body composition, while bioelectrical impedance analysis (BIA) is a validated tool to properly assess nutritional status on a regular basis. Therefore, patient’s monitoring should rely on other affordable indicators such as Karnofsky Performance Status (KPS) and modified Glasgow Prognostic Score (mGPS) to also assess patient’s functional status and prognosis. Finally, catheter-related complications and quality of life represent crucial issues to be monitored over time. The purpose of this narrative review is to describe the role and relevance of monitoring cancer patients on HPN, regardless of whether they are receiving anticancer treatments. These practical tips may be clinically useful to better guide healthcare providers in the nutritional care of these patients.

Value of TAT and PIC with D-dimer for cancer patients with metastasis.

The hypercoagulability of blood is related to the development and metastasis of cancer. High levels of D-dimer have been reported to be associated with the metastasis and poor prognoses of cancer. Here, we investigated the performance of biomarkers-TAT, PIC, TM, and tPAI·C by new method-for monitoring cancer patients with metastasis. A total of 197 cancer patients were enrolled. TM, TAT, PIC, and tPAI·C were detected by the chemiluminescence immunoassay. Results showed that the levels of TAT and PIC were higher in the metastasis group than those in the nonmetastasis group (P<.01). In the nonmetastasis group, there were 16 patients with elevated levels of D-dimer. But, TAT and PIC in these 16 patients were all at normal level (<0.55mg/L FEU). After dilution, D-dimer was also decreased to normal levels in these 16 patients. The ROC was used to show the performance of D-dimer, TAT, and PIC on indicating cancer with metastasis. The AUC of PIC was higher than that of D-dimer (0.825 vs. 0.770). The specificity and PPV of TAT and PIC were higher than those of D-dimer. Serial test of TAT, PIC, and D-dimer improved the specificity and positive predictive value to 90.91% [80.61%, 96.25%] and 89.29% [77.45%, 95.57%], respectively. Combining TAT and PIC with D-dimer could be useful surveillance biomarkers for cancer with metastasis.

Quantification of cobimetinib, cabozantinib, dabrafenib, niraparib, olaparib, vemurafenib, regorafenib and its metabolite regorafenib M2 in human plasma by UPLC-MS/MS.

A sensitive and selective ultra‐high performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method for the simultaneous determination of seven oral oncolytics (two PARP inhibitors, i.e. olaparib and niraparib, and five tyrosine kinase inhibitors, i.e. cobimetinib, cabozantinib, dabrafenib, vemurafenib and regorafenib, plus its active metabolite regorafenib M2) in EDTA plasma was developed and validated. Stable isotope‐labelled internal standards were used for each analyte. A simple protein precipitation method was performed with acetonitrile. The LC–MS/MS system consisted of an Acquity H‐Class UPLC system, coupled to a Xevo TQ‐S micro tandem mass spectrometer. The compounds were separated on a Waters CORTECS UPLC C18 column (2.1 × 50 mm, 1.6 μm particle size) and eluted with a gradient elution system. The ions were detected in the multiple reaction monitoring mode. The method was validated for cobimetinib, cabozantinib, dabrafenib, niraparib, olaparib, vemurafenib, regorafenib and regorafenib M2 over the ranges 6–1000, 100–5000, 10–4000, 200–2000, 200–20,000, 5000–100,000, 500–10,000 and 500–10,000 μg/L, respectively. Within‐day accuracy values for all analytes ranged from 86.8 to 115.0% with a precision of <10.4%. Between‐day accuracy values ranged between 89.7 and 111.9% with a between‐day precision of <7.4%. The developed method was successfully used for guiding therapy with therapeutic drug monitoring in cancer patients and clinical research programs in our laboratory.

A Secure Occupational Therapy Framework for Monitoring Cancer Patients' Quality of Life.

Once diagnosed with cancer, a patient goes through a series of diagnosis and tests, which are referred to as “after cancer treatment”. Due to the nature of the treatment and side effects, maintaining quality of life (QoL) in the home environment is a challenging task. Sometimes, a cancer patient’s situation changes abruptly as the functionality of certain organs deteriorates, which affects their QoL. One way of knowing the physiological functional status of a cancer patient is to design an occupational therapy. In this paper, we propose a blockchain and off-chain-based framework, which will allow multiple medical and ambient intelligent Internet of Things sensors to capture the QoL information from one’s home environment and securely share it with their community of interest. Using our proposed framework, both transactional records and multimedia big data can be shared with an oncologist or palliative care unit for real-time decision support. We have also developed blockchain-based data analytics, which will allow a clinician to visualize the immutable history of the patient’s data available from an in-home secure monitoring system for a better understanding of a patient’s current or historical states. Finally, we will present our current implementation status, which provides significant encouragement for further development.

Opportunities, Challenges, and Prospects in Electrochemical Biosensing of Circulating Tumor DNA and its Specific Features.

Nowadays, analyzing circulating tumor DNA (ctDNA), a very small part of circulating free DNA (cfDNA) carried by blood, is considered to be an interesting alternative to conventional single-site tumor tissue biopsies, both to assess tumor burden and provide a more comprehensive snapshot of the time-related and spatial heterogeneity of cancer genetic/epigenetic scenery. The determination of ctDNA and/or mapping its characteristic features, including tumor-specific mutations, chromosomal aberrations, microsatellite alterations, and epigenetic changes, are minimally invasive, powerful and credible biomarkers for early diagnosis, follow-up, prediction of therapy response/resistance, relapse monitoring, and tracking the rise of new mutant subclones, leading to improved cancer outcomes This review provides an outline of advances published in the last five years in electrochemical biosensing of ctDNA and surrogate markers. It emphasizes those strategies that have been successfully applied to real clinical samples. It highlights the unique opportunities they offer to shift the focus of cancer patient management methods from actual decision making, based on clinic-pathological features, to biomarker-driven treatment strategies, based on genotypes and customized targeted therapies. Also highlighted are the unmet hurdles and future key points to guide these devices in the development of liquid biopsy cornerstone tools in routine clinical practice for the diagnosis, prognosis, and therapy response monitoring in cancer patients.

Monitoring of cancer patients via next-generation sequencing of patient-derived circulating tumor cells and tumor DNA.

Liquid biopsy of circulating tumor cells (CTC) and circulating tumor DNA (ctDNA) is gaining attention as a method for real‐time monitoring in cancer patients. Conventional methods based upon epithelial cell adhesion molecule (EpCAM) expression have a risk of missing the most aggressive CTC subpopulations due to epithelial‐mesenchymal transition and may, thus, underestimate the total number of actual CTC present in the bloodstream. Techniques utilizing a label‐free inertial microfluidics approach (LFIMA) enable efficient capture of CTC without the need for EpCAM expression. In this study, we optimized a method for analyzing genetic alterations using next‐generation sequencing (NGS) of extracted ctDNA and CTC enriched using an LFIMA as a first‐phase examination of 30 patients with head and neck cancer, esophageal cancer, gastric cancer and colorectal cancer (CRC). Seven patients with advanced CRC were enrolled in the second‐phase examination to monitor the emergence of alterations occurring during treatment with epidermal growth factor receptor (EGFR)‐specific antibodies. Using LFIMA, we effectively captured CTC (median number of CTC, 14.5 cells/mL) from several types of cancer and detected missense mutations via NGS of CTC and ctDNA. We also detected time‐dependent genetic alterations that appeared during anti–EGFR therapy in CTC and ctDNA from CRC patients. The results of NGS analyses indicated that alterations in the genomic profile revealed by the liquid biopsy could be expanded by using a combination of assays with CTC and ctDNA. The study was registered with the University Hospital Medical Information Network Clinical Trials Registry (ID: UMIN000014095).

Examining the feasibility, acceptability, and potential utility of mobile distress screening in adult cancer patients.

A common method of distress monitoring in cancer patients relies on static and retrospective data collected in-person at the time of a health care provider appointment. Relatively little work has examined the potential usefulness of mobile distress monitoring using cancer patients' smartphones. The current study deployed longitudinal distress monitoring using secure text messaging. In an observational study, a total of 52 cancer patients receiving active cancer treatment (Mage =58, 62% female) received a text message once a week for 4weeks. Text messages contained a secure link to complete online the Patient Health Questionnaire-4 (PHQ-4), a commonly used distress screener. Cancer patients completed a distress screener 75% of the time they received a text message. On average, it took less than a minute to complete each mobile distress screener. Geolocation data indicated that cancer patients completed distress screeners across a range of locations. Analyses of model fit of distress scores indicated significant heterogeneity in variability of distress scores over time and across cancer patients (AIC=630.5). Quantitative feedback from cancer patients at the end of the study indicated high ease of use, ease of learning, and satisfaction of completing mobile distress screeners. These findings support the use of secure text messaging to monitor longitudinal, out of clinic, distress in cancer patients. Findings also highlight the importance of mobile-based approaches to distress screening in order to maximize opportunities to intervene.

Skin Toxicities with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Cancer Patients: A Meta-Analysis of Randomized Controlled Trials

We fully investigate the skin toxicities of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in cancer patients. The studies about randomized controlled trials in cancer treatment with EGFR-TKIs were retrieved and the systematic evaluation was conducted. The results suggest that EGFR-TKIs significantly increase the risk of skin toxicities including all-grade rash, pruritus, dry skin, and high-grade rash, pruritus. However, the risk of high-grade dry skin did not increase. Rash was the most common toxicity. Physicians should be aware of skin toxicities and should monitor cancer patients when receiving EGFR-TKIs.

Abstract 1352: Serum neurofilament light (NfL), glial fibrillary acidic protein (GFAp) and tau protein are possible serum biomarkers for activity of brain metastases and gliomas

Abstract Introduction: While the morbidity and mortality attributable to gliomas and brain metastases is significant, there are currently no approved biomarkers for detecting and monitoring intracranial disease and imaging remains the primary modality. Blood levels of the neurofilament light (NfL) and tau, as well as glial fibrillary acidic protein (GFAp) show promise as biomarkers for brain injury. We therefore hypothesized that these biomarkers would correlate with CNS activity of gliomas and brain metastases. Methods: Serum concentrtaions of NfL, tau and GFAp were measured using the ultrasensitive single molecule array (Simoa) technology (Quanterix, Lexington, MA). Levels of the three proteins were then correlated with status of gliomas and brain metastases in the patients. Statistical analysis was performed using GraphPad Prism7 and all p-values were 2-tailed with an accepted 2-sided alpha level of 0.05 as statistically significant. Results: 36 patients were enrolled with varying malignancies. Both serum NfL and GFAp levels were significantly associated with the state of intracranial disease (ANOVA psNfL= 0.0307; ANOVA pGFAp=0.0348). In contrast, serum tau levels were discordant with brain involvement with cancer (ANOVA pTau= 0.1453). Conclusion: Serum NfL and GFAp both apparently vary closely with presence and activity of gliomas and brain metastases. Our studies are among the first to identify possible candidate serum biomarkers for screening and monitoring cancer patients for CNS involvement with malignancy. Further studies in larger populations are needed to expand these findings. Citation Format: Jason Porter, Adriana Hepner, Manjari Pandey, Philippe Prouet, Felicia Hare, Syed S. Nasir, Madison Boles, Henrik Zetterberg, Kaj Blennow, Michael Martin. Serum neurofilament light (NfL), glial fibrillary acidic protein (GFAp) and tau protein are possible serum biomarkers for activity of brain metastases and gliomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1352.

Comparison of SUVmax Values Obtained from F-18 FDG PET/CT and Cell-free DNA Levels Measured from Plasma in Oncology Patients

Objectives:The aim of this study was to compare the quantitative value of standardized uptake value (SUV) SUVmax obtained from F-18 FDG positron emission tomography/computed tomography (PET/CT) imaging of oncology patients with the cell-free DNA (cfDNA) amounts measured in plasma of patients and thus investigate if cfDNA is a significant marker to identify the presence of malignancy in the early period.Methods:A total of 184 patients were included in the study. The clinical, histopathologic, laboratory and treatment parameters were extracted from patient files. SUVmax and cfDNA quantities were assessed.Results:There was no statistically significant difference in plasma cfDNA values between patient and control groups. The comparison of SUVmax and cfDNA values in the study showed that there was a weak correlation between SUVmax and cfDNA. There was a significant difference between tumor size and SUVmax values. However, there was no statistically significant difference between tumor size and cfDNA.Conclusion:cfDNA measurements in the blood as a screening test have provided hope for early diagnosis and monitoring of cancer patients. Comparison of cfDNA levels obtained from plasma and quantitative parameters from PET/CT images of oncology patients in detailed advanced studies with larger patient series are required.

Safety of combining vascular endothelial growth factor receptor tyrosine-kinase inhibitors with chemotherapy in patients with advanced non-small-cell lung cancer: A PRISMA-compliant meta-analysis.

Background:Vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs) have been developed for targeted therapies in non–small-cell lung cancer (NSCLC); moreover, some drug-related toxic reactions among cancer patients have been reported. A meta-analysis of randomized controlled trials (RCTs) to definite the incidence and the risk of grade ≥3 adverse events (AEs), serious and fatal AEs (SAEs and FAEs), with VEGFR-TKIs in advanced/metastatic NSCLC patients was performed.Methods:A comprehensive literature search was conducted for the clinical trials published up to December 2017. Qualified studies allotted patients with advanced/metastatic NSCLC to receive either chemotherapy alone or in combination with VEGFR-TKIs. Data were extracted by 2 authors.Results:Eighteen RCTs of VEGFR-TKIs plus chemotherapy, involving 8461 advanced NSCLC patients were included. The proportion of patients with grade ≥3 AEs was increased with the addition of VEGFR-TKIs (relative risk, 1.35; 95% confidence interval [CI] 1.19–1.52; incidence, 68.1% vs 50.1%; P < .001). The most common grade ≥3 AEs was neutropenia (24.9% vs 15.4%, P < .001). Addition of VEGFR-TKIs was also related to the increased risk of SAEs (relative risk, 1.34; 95% CI 1.14–1.56; incidence, 37.8% vs 27.9%; P < .001) and FAEs (relative risk, 2.16, 95% CI 1.47–3.19; incidence, 3.4% vs 1.8%). Subgroup analysis suggested there was no difference in the rates of SAEs and FAEs in the second-line settings. No evidence of bias was found between the literatures. The study was registered with PROSPERO (CRD42018099654).Conclusions:In comparison with chemotherapy alone, the addition of VEGFR-TKIs in advanced NSCLC patients was related to the increased risk of grades ≥3 AEs, SAEs, and FAEs, especially in the first-line settings. Physicians should be aware of some specific grade ≥3 adverse effect, especially haematologic adverse events, and it is also necessary to monitor cancer patients receiving VEGFR-TKIs.

DNA damage and repair measured by comet assay in cancer patients

The last decade witnessed an increase in the use of comet assay for DNA damage monitoring in cancer patients and controls. Apart from case-control studies, reports described the determination of DNA damage prior to (baseline value) and after chemo-/radiotherapy, the treatment resulted in significantly elevated DNA damage. However, studies on DNA damage as a factor reflecting cancer prognosis and therapy prediction are scarce. In most cases, DNA damage was analysed in surrogate tissues. The data on DNA damage are available for 17 types of cancer. The reviewed data unambiguously pinpoint the usefulness of the comet assay in human cancer research due to its sensitivity and cost-effectiveness in evaluating DNA damage associated with the disease and with the treatment.DNA repair capacity (DRC) represents a complex marker for functional evaluation of multigene DNA repair processes in cancer onset with future prospects in personalized prevention and/or cancer treatment. A comparison between studies and more general conclusions are precluded by a variable design of the studies and a lack of standard protocol for both DNA damage and DRC determination. Since cancer is a heterogeneous complex disease, numerous points have to be considered: a) DNA damage and DRC measured in surrogate/target tissues, b) changes in the levels of DNA damage and DRC may be a cause or a consequence of the disease, c) changes in DRC alter sensitivity of tumour cells to antineoplastic drugs, d) one time point-sampling of patients provides insufficient information on the role of DNA damage and its repair in carcinogenesis. Finally, systemic cancer therapy is targeted at DNA damage and its repair. A proper understanding of these processes is a key precondition for the optimisation of therapy regimens, prediction of therapeutic response and prognosis in cancer patients.