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• Proposing a deep RL-based controller for cancer chemotherapy, which handles states and action in infinite space. • The proposed approach does not need to have a mathematical model of the system, it just needs to have tumor volume. • Providing an adaptive control technique to respond to the special conditions and diagnosis measurements of different categories of patients. • Evaluating and comparing the efficiency and robustness of the proposed method using patients with diverse conditions. Advancement in the treatment of cancer, as a leading cause of death worldwide, has promoted several research activities in various related fields. The development of effective treatment regimens with optimal drug dose administration using a mathematical modeling framework has received extensive research attention during the last decades. However, most of the control techniques presented for cancer chemotherapy are mainly model-based approaches. The available model-free techniques based on Reinforcement Learning (RL), commonly discretize the problem states and variables, which other than demanding expert supervision, cannot model the real-world conditions accurately. The more recent Deep Reinforcement Learning (DRL) methods, which enable modeling the problem in its original continuous space, are rarely applied in cancer chemotherapy. In this paper, we propose an effective and robust DRL-based, model-free method for the closed-loop control of cancer chemotherapy drug dosing. A nonlinear pharmacological cancer model is used for simulating the patient and capturing the cancer dynamics. In contrast to previous work, the state variables and control action are modeled in their original infinite spaces to avoid expert-guided discretization and provide a more realistic solution. The DRL network is trained to automatically adjust the drug dose based on the monitored states of the patient. The proposed method provides an adaptive control technique to respond to the special conditions and diagnosis measurements of different categories of patients. The performance of the proposed DRL-based controller is evaluated by numerical analysis of different diverse simulated patients. Comparison to the state-of-the-art RL-based method, which uses discretized state and action spaces, shows the superiority of the approach in the process and duration of cancer chemotherapy treatment. In the majority of the studied cases, the proposed model decreases the medication period and the total amount of administrated drug, while increasing the rate of reduction in tumor cells. [ABSTRACT FROM AUTHOR]

A large number of inorganic and organic compounds is able to bind to DNA and form complexes. Among them, drugs I are very important, especially chemotherapeutics. This paper presents the overview of DNA structural characteristics and types of interactions (covalent and non-covalent) between DNA molecule and drugs. Covalent binding of the drug is irreversible and leads to complete inhibition of DNA function, what conclusively, causes the cell death. On the other hand, non-covalent binding is reversible and based on the principle of molecular recognition. Special attention is given to elucidation of the specific sites in DNA molecule for drug binding. According to their structural characteristics, drugs that react non-covalently with DNA are mainly intercalators, but also minor and major groove binders. When the complex between drug and DNA is formed, both the drug molecule, as well as DNA, experienced some modifications. This paper presents the overview of the methods used for the study of the interactions between DNA and drugs with the aim of detection and explanation of the resulting changes. For this purpose many spectroscopic methods like UV/VIS, fluorescence, infrared and NMR, polarized light spectroscopies like circular and linear dichroism, and fluorescence anisotropy or resonance is used. The development of the electrochemical DNA biosensors has opened a wide perspective using particularly sensitive and selective electrochemical methods for the detection of specific DNA interactions. The presented results summarize literature data obtained by the mentioned methods. The results are used to confirm the DNA damage, to determine drug binding sites and sequence preference, as well as conformational changes due to drug-DNA interaction. [ABSTRACT FROM AUTHOR]

Chemotherapy services in the UK have been the subject of national policy directives for the past decade. These directives, amongst other things, include the development of nurseled services; however, progress has been slow. This paper looks at the evidence for nurse-led services and discusses the competencies and skills required. Chemotherapy nurses have been much respected for their drug knowledge, information-giving, and communication skills, but in the past have lacked assessment skills. This paper offers a guide to assessment of chemotherapy patients, including the process of chemotherapy, key information needs, and consent, taking account of the recent 2013 National Cancer Patient Experience Survey. It discusses in detail the common side effects of treatment and their management, outlining international common toxicity criteria to guide assessment. Finally, it briefly outlines a new initiative of acute oncology services that have enhanced not only the quality of services but the safety of patients receiving chemotherapy. [ABSTRACT FROM AUTHOR]

We observed 10.3% cases of ischemia in our patients during 5-FU infusion; in nearly half it was effort-induced (asymptomatic in 68%, and with severe arrhythmias in 15%). The only predictive factors were atypical symptoms during daily life. Silent and effort ischemia may be easily underdiagnosed. A practical screening flow-chart using stress-test is suggested.Background Effort-induced myocardial ischemia (EMI) has been seldom described. Aims of our study were (A) to evaluate the prevalence of EMI during long-lasting 5-FU infusion; (B) to identify possible risk factors of EMI during 5-FU infusion. Patients and methods For the purpose (A), we prospectively evaluated a group of patients undergoing in-hospital continuous infusion (c.i.) of 5-FU. Patients with rest ischemia were excluded. Among 358 consecutive patients, 21 (5.9%) had rest ischemia; 109 could not perform a stress test. The remaining 228 patients underwent a treadmill stress test (TST) after >46 h of 5-FU infusion. For the purpose (B), we compared the characteristics of patients with EMI (including 3 previously described in a 2001 paper) with those without EMI. Results Among 228 patients, 16 (6.9%) had EMI. These 16 had a second TST after stopping 5-FU: in 14, it was negative, 2 patients with coronary artery disease had milder ischemia. The whole group of 231 (including 3 described in a previous paper) patients undergoing TST included 148 males and 83 females, with mean age of 57.5. Cardiovascular risk factors were present in 178 of them. Eight patients had ischemic heart disease. Among 19 patients with EMI, 7 had angina, 12 silent ischemia. ST segment at ECG was elevated in 10 patients, depressed in 9. Comparing the group with toxicity and the one without, the only significant difference was the complaint of atypical symptoms at rest before the TST. No difference was observed as regards: chemotherapy schedule (chronic c.i. in 49, 5 days in 178, FOLFOX type in 12), coronary risk factors or heart disease. Conclusions EMI is as frequent as rest ischemia during 5-FU infusion. Patients undergoing 5-FU continuous infusions should be adviced to avoid unusual efforts, to refer any cardiac symptom, and should be investigated for EMI. [ABSTRACT FROM PUBLISHER]

Electrochemotherapy is a local treatment of cancer employing electric pulses to improve transmembrane transfer of cytotoxic drugs. In this paper we discuss electrochemotherapy from the perspective of biomedical engineering and review the steps needed to move such a treatment from initial prototypes into clinical practice. In the paper also basic theory of electrochemotherapy and preclinical studies in vitro and in vivo are briefly reviewed. Following this we present a short review of recent clinical publications and discuss implementation of electrochemotherapy into standard of care for treatment of skin tumors, and use of electrochemotherapy for other targets such as head and neck cancer, deep-seated tumors in the liver and intestinal tract, and brain metastases. Electrodes used in these specific cases are presented with their typical voltage amplitudes used in electrochemotherapy. Finally, key points on what should be investigated in the future are presented and discussed. [ABSTRACT FROM AUTHOR]

Abstract: Treatment options targeting laryngeal preservation include conservative surgery, concurrent chemo-radiotherapy, induction chemotherapy (IC) followed by radiotherapy (RT), and alternating chemo-radiation. The goal of this paper was to perform a systematic review of randomized clinical trials (RCTs) on current and emerging approaches in the field of larynx preservation. The search identified 36 papers of which 27 did not fall within the inclusion criteria (i.e. non-RCTs). IC followed by RT has been shown to allow laryngeal preservation in about two-thirds of pts with locally advanced laryngeal or hypopharyngeal cancer without compromising survival. IC is regarded as the landmark treatment of non-surgical larynx preservation approaches. Concomitant and alternating chemoradiotherapy treatments are also acceptable in larynx preservation. [Copyright &y& Elsevier]

Acute leukemias of ambiguous lineage, not otherwise specified (ALAL-NOS) is a rare type of acute leukemia. Management of relapse/refractory (R/R) patients is still challenging.traditional chemotherapy treatment is not effective. In this paper, we reported 6 R/R patients diagnosed as ALAL-NOS in our hospital, who were treated with venetoclax based treatment (venetoclax combining with azacitidine or chemotherapy). All 6 patients achieved CR. Five of the six patients received allo-HSCT, four patients were still alive in CR until the follow-up day. Our data provide preliminary evidence and show that venetoclax based regimens are effective and safety in patients with R/R ALAL-NOS. [ABSTRACT FROM AUTHOR]

Aims The aim of this paper was to update the evidence-based practice guidelines for the nutritional management of patients receiving radiation therapy and broaden the scope to include chemotherapy. Methods The following databases were searched using a range of keywords: Cochrane Database, CENTRAL, MEDLINE (via Ebscohost), EMBASE, CINAHL ( Ebscohost), Web of Science, Health Source: Nursing/ Academic Edition and Pub Med. Relevant papers (n = 47) were reviewed by at least two members of the steering committee and assigned a level of evidence and a quality rating. Results There were no new published randomised controlled trials ( RCTs) of nutrition intervention in radiation therapy. Most statements in the previous radiation therapy guidelines have strong evidence supporting nutrition intervention. There were 12 studies in chemotherapy including five RCTs. While these studies provided strong evidence that simple nutrition intervention improves nutritional outcomes such as dietary intake and weight, they did not find an improvement in quality of life or survival. Several RCTs found no benefits of nutrition support in patients undergoing chemotherapy. None of the RCTs in chemotherapy used medical nutrition therapy ( MNT) as the intervention, but rather simple dietary advice and/or supplements. Conclusions The evidence to support nutrition intervention in patients receiving radiation therapy remains strong. However, the benefits of nutrition intervention in chemotherapy are less clear. Further studies are required to evaluate the impact of MNT as opposed to simple dietary advice in chemotherapy patients. This update contributes to a move towards comprehensive evidence-based guidelines for the nutritional management of patients with cancer. [ABSTRACT FROM AUTHOR]

Our institution performs chemotherapy/immunotherapy competency verification on an annual basis for nursing via in person simulation of chemotherapy specific skills. In previous years, live simulation was done with our team of nursing professional development specialists (NPDS). During the 2020 COVID-19 pandemic, we adjusted the competency to a paper format for social distancing compliance. Feedback around the paper format was mixed, yielding a change for 2021. Utilizing technology to its fullest, we opted to transition the activity to a digital Learning Management System (LMS) platform. The purpose of this project was to implement an electronic process for validating competency of nurses who handle chemotherapy/immunotherapy. The goal is to provide easy accessibility to ensure that nurses have completed the competency requirements within the deadline and provide instant continuing education (CE) credits. The NPDS team met and reviewed feedback from the 2020 competency program to determine the best way to proceed in 2021, providing a high quality experience while maintaining social distancing protocols. Consensus was obtained to proceed with an on demand LMS module. After a careful review of safety events reported along with trends identified by NPDS as a knowledge gap, topics were selected to be the focus of 2021's chemo/immunotherapy competency. Independent verification at the bed/chairside, hazardous drug spills, sexual and reproductive health during treatment, and order set verification were identified as priority topics. Each participant will receive a link to a survey upon completion of the LMS module. Results will be tabulated and reviewed by the NPDS team to compare to previous models of competency assessment. This project was designed using the data collected in during the 2020 assessment to meet the needs created by the changing landscape of the Covid 19 pandemic. The aim is to continue to share and evaluate how we have evolved the delivery of high quality content on an annual basis. The collation of data from this year's competency will be compared with previous years and used to help us grow and develop our annual competency verification program. Using technology to assess annual chemotherapy/immunotherapy competency by building a module within our existing LMS platform. This innovation will allow for easier use for nurses and easier compliance tracking / CE dissemination for NPDS. [ABSTRACT FROM AUTHOR]

Purpose: Deoxyribonucleic acid is wrapped around an octamer of core histone proteins to form a nucleosome, the basic structure of chromatin. Two main families of enzymes maintain the equilibrium of acetyl groups added to or removed from lysine residues. Histone deacetylases (HDACs) catalyze the removal of acetyl groups from lysine residues in histone amino termini and non-histone proteins also, leading to chromatin condensation and transcriptional repression. HDAC overexpression, resulting in tumor suppressor genes silencing, has been found in several human cancer tissues, indicating that aberrant epigenetic activity is associated with cancer development. Therefore, inhibitors of these enzymes are emerging anticancer agents and there is evidence supporting their role in hematological malignancies. The minimal efficacy of conventional chemotherapy has prompted a renewed focus on targeted therapy based on pathways altered during the pathogenesis of lung cancer. We identify the pleiotropic antitumor effects of HDAC inhibitors in lung cancer, focusing on the result caused by their use individually, as well as in combination with other chemotherapeutic agents, in lung cancer cell lines and in clinical trials. Method: We searched reviews and original papers in Pubmed over the last 10 years. Results: We identified 76 original papers on this topic. Conclusions: Numerous preclinical studies have shown that HDAC inhibitors exhibit impressive antitumor activity in lung cancer cell lines. Nevertheless, Phase III randomized studies do not support HDAC inhibitors use in lung cancer patients in everyday practice. Ongoing and future studies would help determine their role in lung cancer treatment. [ABSTRACT FROM AUTHOR]

This paper describes how we applied simulation and optimization in combination to improve patient flow within the Duke Cancer Institute, a large cancer center. We first developed a discrete-event simulation model to predict patient waiting time and resource utilization throughout various parts of the center, including the outpatient clinic, radiology, the pharmacy, laboratory services, and the oncology treatment facility. Simulation model studies showed that nurse unavailability during oncology treatment causes a serious bottleneck in patient flow. Next, we developed a mixed-integer programming model to relieve the bottleneck by optimizing weekly and monthly scheduling of different types of nurses. Finally, we developed a novel simulation-optimization model to further relieve the bottleneck by optimizing the starting times of nurse shifts. Our paper summarizes our main findings and the resulting recommendations that Duke Cancer Institute implemented. [ABSTRACT FROM AUTHOR]

Nonlocal calculus is often overlooked in the mathematics curriculum. In this paper we present an interesting new class of nonlocal problems that arise from modelling the growth and division of cells, especially cancer cells, as they progress through the cell cycle. The cellular biomass is assumed to be unstructured in size or position, and its evolution governed by a time-dependent system of ordinary differential equations with multiple time delays. The system is linear and taken to be autonomous. As a result, it is possible to reduce its solution to that of a nonlinear matrix eigenvalue problem. This method is illustrated by considering case studies, including a model of the cell cycle developed recently by Simms, Bean and Koeber. The paper concludes by explaining how asymptotic expressions for the distribution of cells across the compartments can be determined and used to assess the impact of different chemotherapeutic agents. [ABSTRACT FROM AUTHOR]

Background: Intervention-generated inequalities are unintended variations in outcome that result from the organisation and delivery of health interventions. Socioeconomic inequalities in treatment may occur for some common cancers. Although the incidence and outcome of lung cancer varies with socioeconomic position (SEP), it is not known whether socioeconomic inequalities in treatment occur and how these might affect mortality. We conducted a systematic review and meta-analysis of existing research on socioeconomic inequalities in receipt of treatment for lung cancer. Methods and Findings: MEDLINE, EMBASE, and Scopus were searched up to September 2012 for cohort studies of participants with a primary diagnosis of lung cancer (ICD10 C33 or C34), where the outcome was receipt of treatment (rates or odds of receiving treatment) and where the outcome was reported by a measure of SEP. Forty-six papers met the inclusion criteria, and 23 of these papers were included in meta-analysis. Socioeconomic inequalities in receipt of lung cancer treatment were observed. Lower SEP was associated with a reduced likelihood of receiving any treatment (odds ratio [OR] = 0.79 [95% CI 0.73 to 0.86], p,0.001), surgery (OR = 0.68 [CI 0.63 to 0.75], p,0.001) and chemotherapy (OR = 0.82 [95% CI 0.72 to 0.93], p = 0.003), but not radiotherapy (OR = 0.99 [95% CI 0.86 to 1.14], p = 0.89), for lung cancer. The association remained when stage was taken into account for receipt of surgery, and was found in both universal and non-universal health care systems. Conclusions: Patients with lung cancer living in more socioeconomically deprived circumstances are less likely to receive any type of treatment, surgery, and chemotherapy. These inequalities cannot be accounted for by socioeconomic differences in stage at presentation or by differences in health care system. Further investigation is required to determine the patient, tumour, clinician, and system factors that may contribute to socioeconomic inequalities in receipt of lung cancer treatment. [ABSTRACT FROM AUTHOR]

This paper reviews the contribution of chemotherapy in the conquest of osteosarcoma. It discusses how the treatment of osteosarcoma has evolved over the last five decades, resulting in a more than fivefold increase in survival. Though the initial improvements in survival were dramatic, essentially there has been no change in the outlook for this disease over the past 30 years. The paper also highlights the necessity of a multidisciplinary approach to combat this disease and stresses the need to explore newer treatment agents in order to build on the lessons learnt from the past while striving to achieve greater levels of success. [ABSTRACT FROM AUTHOR]

Abstract: A best evidence topic in surgery was written according to a structured protocol. The question addressed was whether patients who have undergone chemoradiotherapy (CRT) for locally advanced squamous cell carcinoma of the oesophagus benefit from surgical resection. 505 papers were found using the reported search, of which 5 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group, study type, relevant outcomes and results of these papers are tabulated. Of these five studies, two were randomised controlled trials. These demonstrated that there was no survival benefit in adding surgery to patients who have undergone CRT for oesophageal cancer. The remaining three observational studies suggest that surgery may have a prognostic benefit for patients who show a partial, but not complete response to CRT. We conclude that for patients who are complete responders to induction CRT, surgery adds no survival benefit. With regard to partial responders there is weak evidence suggesting that there may be some benefit in surgery after CRT, but further trials are needed to clarify the survival benefit (if any) of adding oesophagectomy to CRT for this sub-group. [Copyright &y& Elsevier]

Abstract: Background: Evaluation of new therapies for cancer has suffered a paradigm shift in the last years. The use of innovative and more efficient designs is a priority for the scientific community; nevertheless, the use of this kind of design is not yet wide spread. Purpose: In this paper will examine the effectiveness of adaptive designs compared with traditional designs in phase II clinical trials. Methods: We reviewed a group of abstracts records between 1980 and 2008 and extracted data regarding statistical design, year of publication, kind of evaluated product, localization, sample size and results of the trials. Results: Nine hundred and eighty-nine clinical trials were identified and from them 333 traditional designs and 19 adaptive designs were included in the review. Two hundred statistical papers were located and 16 were included in the review. The most frequent designs were Standard up and down designs, continual reassessment methods and its variation and designs with Bayesian approaches. More than 80% of the studies evaluated different schemes of chemotherapy. Adaptive designs evaluated only drugs and not any kind of treatment combination and the most often localizations evaluated in both designs were lung, haematology malignancies, and colon cancers. Conclusions: Adaptive designs are more efficient from the statistical point of view but they are not yet widely used because of complex and computationally intensive methods needed, substantial effort for planning the trials and lack of regulatory guidance. [Copyright &y& Elsevier]

Ovarian cancer is a common cause of cancer mortality in women with limited treatment effectiveness in advanced stages. The limitation to treatment is largely the result of high rates of cancer recurrence despite chemotherapy and eventual resistance to existing chemotherapeutic agents. The objective of this paper is to review current concepts of ovarian carcinogenesis. We will review existing hypotheses of tumor origin from ovarian epithelial cells, Fallopian tube, and endometrium. We will also review the molecular pathogenesis of ovarian cancer which results in two specific pathways of carcinogenesis: (1) type I low-grade tumor and (2) type II high-grade tumor. Improved understanding of the molecular basis of ovarian carcinogenesis has opened new opportunities for targeted therapy. This paper will also review these potential therapeutic targets and will explore new agents that are currently being investigated. [ABSTRACT FROM AUTHOR]

Squamous cell carcinoma of head and neck (SCCHN) is the most common neoplasm of the upper aerodigestive tract. In this paper, we attempt to summarize the role and applications of the epidermal growth factor receptor (EGFR) inhibitors monoclonal antibodies (moAbs) and tyrosine kinase inhibitors (TKIs) locally advanced as well as metastatic SCCHN. Targeted therapy in SCCHN is now incorporated in the first-line regimes for advanced disease. Novel targeted agents, including the EGFR antibody, cetuximab, have been approved for use as single agents or in combination with radiation therapy or chemotherapy in treatment of recurrent metastatic or locally advanced SCCHN. Refractory mechanisms that bypass the pathway of EGFR inhibitors activity are identified explaining resistance to targeted therapy. Strategies of cotargeting EGFR and other pathways are under investigation. Examples of targeted therapy being used include mammalian target of rapamycin (mtor) inhibitors, antivascular endothelial growth factor (VEGF) moAb, and other inhibitors. We will be focusing our paper on the preclinical and clinical aspects of EGFR inhibition in SCCHN and touch upon other targeted therapies in application. [ABSTRACT FROM AUTHOR]

Thyroid cancer is the most common endocrine tumor. Thyroidectomy, radioactive iodine, and TSH suppression represent the standard treatment for differentiated thyroid cancer. Since chemotherapy has been shown to be unsuccessful in case of advanced thyroid carcinomas, the research for new therapies is fundamental. In this paper, we reviewed the recent literature reports (pubmed, medline, EMBASE database, and abstracts published in meeting proceedings) on new treatments in advanced nonmedullary and medullary thyroid carcinomas. Studies of many tyrosine kinase inhibitors as well as antiangiogenic inhibitors suggest that patients with thyroid cancer could have an advantage with new target therapy. We summarized both the results obtained and the toxic effects associated with these treatments reported in clinical trials. Reported data in this paper are encouraging, but further trials are necessary to obtain a more effective result in thyroid carcinoma treatment. [ABSTRACT FROM AUTHOR]

Background: Anti-cancer therapy is often a cause of premature ovarian insufficiency and infertility since the ovarian follicle reserve is extremely sensitive to the effects of chemotherapy and radiotherapy. While oocyte, embryo and ovarian cortex cryopreservation can help some women with cancer-induced infertility achieve pregnancy, the development of effective methods to protect ovarian function during chemotherapy would be a significant advantage.Objective and Rationale: This paper critically discusses the different damaging effects of the most common chemotherapeutic compounds on the ovary, in particular, the ovarian follicles and the molecular pathways that lead to that damage. The mechanisms through which fertility-protective agents might prevent chemotherapy drug-induced follicle loss are then reviewed.Search Methods: Articles published in English were searched on PubMed up to March 2019 using the following terms: ovary, fertility preservation, chemotherapy, follicle death, adjuvant therapy, cyclophosphamide, cisplatin, doxorubicin. Inclusion and exclusion criteria were applied to the analysis of the protective agents.Outcomes: Recent studies reveal how chemotherapeutic drugs can affect the different cellular components of the ovary, causing rapid depletion of the ovarian follicular reserve. The three most commonly used drugs, cyclophosphamide, cisplatin and doxorubicin, cause premature ovarian insufficiency by inducing death and/or accelerated activation of primordial follicles and increased atresia of growing follicles. They also cause an increase in damage to blood vessels and the stromal compartment and increment inflammation. In the past 20 years, many compounds have been investigated as potential protective agents to counteract these adverse effects. The interactions of recently described fertility-protective agents with these damage pathways are discussed.Wider Implications: Understanding the mechanisms underlying the action of chemotherapy compounds on the various components of the ovary is essential for the development of efficient and targeted pharmacological therapies that could protect and prolong female fertility. While there are increasing preclinical investigations of potential fertility preserving adjuvants, there remains a lack of approaches that are being developed and tested clinically. [ABSTRACT FROM AUTHOR]

The present study was aimed to explore the current practices related to oral chemotherapy prescription, dispensing, monitoring and patient education. The novelty of this study was based in utilizing most recent data for retrieving relevant outcomes. A cross-sectional design was employed to recruit 161 pharmacists, physicians, and nurses. A survey questionnaire was implemented to examine prescribing practices, coordinating and monitoring adherence, safety monitoring, and education of patients regarding oral chemotherapy. Descriptive statistics and Chi-square analysis were used to present data through Statistical Package of Social Sciences software. A majority of the healthcare providers (79 %) received training on the safe handling of oral chemotherapy, while 74 % were trained by their organization regarding patient education. While 68 % of hospitals used self-designed papers as resources to guide patient education, 51 % used drug pamphlets and 16 % used personalized treatment calendars. Almost 94 % of hospitals applied double checks for calculated doses as additional safety technique; while, other hospitals (34 %) used barcode scanning. The future planning and implementation of oral chemotherapy needs proper educational and training for the healthcare workers. In addition, health care workers should follow guidelines for quality assurance of their prescriptions. [ABSTRACT FROM AUTHOR]

• A new method is proposed to determine drug dose for mixed therapy in cancer treatment. • Optimal drug dose for treatment of reference patient is determined via SDRE method. • The SDRE based MRAC design method is introduced for nonlinear MIMO systems. • Personalized drug delivery for an unknown patient is determined using the MRAC method. • The continuous and bang-bang drug delivery protocols are achieved and compared. The paper presents Model Reference Adaptive Control (MRAC) design strategy to determine personalized drug delivery protocol for mixed therapy with chemotherapy and immunotherapy in cancer treatment. We consider a nonlinear mathematical ODE set for cancer dynamics that includes tumor, natural killers, circulating lymphocytes and cytotoxic T-cells population together with the interaction of chemotherapy and immunotherapy. For researchers and physicians, the main challenge in mathematical models is the determination of the exact model parameters. In order to have a drug administration policy for a patient with unknown parameter set, we develop State Dependent Riccati Equations (SDRE) based MRAC design approach to determine the personalized drug delivery protocol for patients with unknown model parameters. First of all, we determine the optimal drug delivery scenario for a reference patient with known dynamics parameters using SDRE approach. Then for any patient with unknown parameters, the personalized mixed therapy protocol is determined based on the treatment regimen of the reference patient. In the proposed methodology, unknown patients are considered as a black-box simulator in the design and the mathematical model parameters of the patient are not essential for the design of drug administration protocol. In addition, the Bang-Bang and continuous drug delivery regimens could be obtained using proper adaptation gains in the presented MRAC methodology. The simulation results demonstrate the effectiveness of the proposed MRAC approach for prescribing a treatment regimen of chemo-immunotherapy. [ABSTRACT FROM AUTHOR]

Chemotherapy‐induced peripheral neurotoxicity (CIPN) is a major toxicity of cancer treatment, leading to dose reduction and premature treatment cessation, potentially affecting patient function, and quality of life. The development of accurate and sensitive assessment tools for CIPN is essential to enable clinical monitoring during treatment, follow‐up of long‐term outcomes and measurement of toxicity in clinical trials. This review examines CIPN clinical assessment scales incorporating clinician‐based, composite, and patient‐reported outcomes (PROs), providing a systematic review of their properties and an updated critical analysis of recommendations on current evidence for their use. This systematic review of CIPN assessment tools identified 50 papers containing 41 assessment tools, across 4 categories (common toxicity criteria; composite neurological scale; PROs; pain scale). The majority of these tools were PROs, underscoring the importance of patient‐based assessment of symptoms. While there has been considerable work in the field over the past 10 years, this review highlights significant gaps, including a lack of evaluation of responsiveness and problematic neuropathic pain evaluation. There remains a need for consensus on the best available tool and the need to modify existing instruments to improve utility. [ABSTRACT FROM AUTHOR]

Soft tissue sarcomas (STS) comprise a heterogeneous and rare group of tumors derived from mesenchymal cells that can rise in any anatomic site and present with diverse biological behaviors. Radical surgery was a common procedure for STS and used to be the standard treatment for many years. However, despite good results regarding local control (LC), it had poor functional outcomes. Nowadays amputations are rarely needed, and the treatment is always multidisciplinary. Many papers have been published on the use of conservative surgery (CS) associated with adjuvant treatments using radiotherapy (RT) and chemotherapy (CT), reporting the possibility of avoiding radical surgeries, maintaining the same results of LC and better quality of life than amputations. Exclusive resection is indicated in lowgrade superficial tumors or in small intramuscular tumors. There are benefits of using neoadjuvant and adjuvant RT; however neoadjuvant RT is associated with a higher incidence of healing difficulties, while adjuvant RT is associated with a higher incidence of fibrosis. RT is indicated for almost all cases of STS. Advanced technology RT is associated with greater LC and lower morbidity than conventional RT and brachytherapy (BRT). CT is not routinely used adjutancy but may be employed in highgrade tumors, or tumors greater than 5 cm. Neoadjuvant CT may have benefits through early treatment of micrometastases and increased resectability rates. New drugs such as targeted therapy, monoclonal antibodies and immunotherapy are under investigation. [ABSTRACT FROM AUTHOR]

• Candida auris is a difficult to detect pathogen that is resistant to many antifungals. • Outbreak measures and screening should be instigated on detection of a first case. • It is critical to use environmental hygiene and effective decontamination methods. • Staff education on control measures for Candida auris is vital to drive best practice. • Formation of environmental biofilms means that disinfectant efficacy may be affected. Candida auris (C. auris) is an emerging fungal pathogen causing invasive infections and outbreaks that have been difficult to control in healthcare facilities worldwide. There is a lack of current evidence for pragmatic infection prevention and control recommendations. The aim of this paper was to review the epidemiology of C. auris and identify best practices with a panel of experts, in order to provide guidance and recommendations for infection prevention and control measures based on available scientific evidence, existing guidelines and expert opinion. The Infection Prevention and Control working group of the International Society of Antimicrobial Chemotherapy organised an expert meeting with infection prevention and mycology experts to review recommendations for healthcare workers on infection prevention and control measures for C. auris at inpatient healthcare facilities. The most common interventions included: screening, standard precautions, cleaning and disinfection, inpatient transfer, outbreak management, decolonisation, and treatment. [ABSTRACT FROM AUTHOR]

Marginal structural models are causal models designed to adjust for time-dependent confounders in observational studies with dynamically adjusted treatments. They are robust tools to assess causality in complex longitudinal data. In this paper, a marginal structural model is proposed with an innovative dose-delay joint-exposure model for Inverse-Probability-of-Treatment Weighted estimation of the causal effect of alterations to the therapy intensity. The model is motivated by a precise clinical question concerning the possibility of reducing dosages in a regimen. It is applied to data from a randomised trial of chemotherapy in osteosarcoma, an aggressive primary bone-tumour. Chemotherapy data are complex because their longitudinal nature encompasses many clinical details like composition and organisation of multi-drug regimens, or dynamical therapy adjustments. This manuscript focuses on the clinical dynamical process of adjusting the therapy according to the patient's toxicity history, and the causal effect on the outcome of interest of such therapy modifications. Depending on patients' toxicity levels, variations to therapy intensity may be achieved by physicians through the allocation of either a reduction or a delay of the next planned dose. Thus, a negative feedback is present between exposure to cytotoxic agents and toxicity levels, which acts as time-dependent confounders. The construction of the model is illustrated highlighting the high complexity and entanglement of chemotherapy data. Built to address dosage reductions, the model also shows that delays in therapy administration should be avoided. The last aspect makes sense from the cytological point of view, but it is seldom addressed in the literature. [ABSTRACT FROM AUTHOR]

Aim The aim of this meta-analysis is to review the morbidity and mortality associated with primary cytoreductive surgery (PCS) compared to neoadjuvant chemotherapy and interval cytoreductive surgery (NACT + ICS) for advanced ovarian cancer. A literature search was performed for publications reporting morbidity and mortality in patients undergoing PCS compared to NACT + ICS. Databases searched were Cochrane, Medline, Pubmed, Pubmed Central, clinicaltrials.gov and Embase. Two independent reviewers applied inclusion and exclusion criteria to select included papers, with differences agreed by consensus. A total of 1341 citations were reviewed; 17 studies comprising 3759 patients were selected for the analysis. The literature search was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results were reported as mean differences or pooled odds ratios (OR) with 95% confidence intervals (95% CI). Patients in the PCS group were significantly more likely to have a Clavien-Dindo grade ≥ 3 morbidity with an overall rate of 21.2% compared to 8.8% (95%CI 1.9–4.0, p < 0.0001) and were more likely to die within 30 days of surgery (OR 6.1, 95% CI 2.1–17.6, p = 0.0008). Patients who underwent NACT + ICS had significantly shorter procedural times (MD −35 min, p = 0.01), lost less blood intraoperatively (MD-382 ml, p < 0.001) and had an average admission 5.0 days shorter (MD −5.0 days, 95% CI −8.1 to −1.9 days, p = 0.002) than those undergoing PCS. While NACT was associated with significantly increased optimal and complete cytoreduction rates (OR 1.9, 95% CI 1.3–2.9, p = 0.001, and OR 2.2, 95% CI 1.5–3.3, p = 0.0001 respectively), this did not confer any additional survival benefit (OR 1.0, p = 0.76). NACT is associated with less morbidity and mortality and improved complete cytoreduction compared to PCS, with no survival benefit. Hence NACT is an acceptable alternative in selected patients in particular with medical co-morbidities or a high tumour burden. • Primary cytoreductive surgery (PCS) associated with a 20% morbidity rate compared to 8% in neoadjuvant chemotherapy (NACT) • NACT associated with increased optimal cytoreduction rates but no difference in overall or progression free survival. • PCS should remain standard of care where complete gross resection is achievable. [ABSTRACT FROM AUTHOR]

Purpose: Purposes are (1) to measure main radiation parameters and (2) to propose a method to estimate the absorbed doses of internal organs starting from DAP values. Measuring the exposition of internal organs by repeated irradiations on an anthropomorphic phantom with the same settings used in vivo, we could establish correlations between (1) DAP and the dose recorded by a dosimeter placed along the X-ray beam entrance pathway; (2) the dose recorded by the same dosimeter and the absorbed dose in internal organs. Methods: Forty-four consecutive patients (16 males, 28 females) (mean age 35.4 months) treated at our institution with IAC (216 procedures: 196 via the ICA and 20 into branches of the ECA) were included in this prospective study. IAC was divided into 5 phases. Fluoroscopic time, DAP, and ESD were measured. Results: The mean DAP was 595 ± 445 cGy cm2 and the mean fluoroscopic time was 540 ± 403 s. ESD was on average 9.59 mGy (range 0.8–165 mGy). The absorbed dose was lower than 12.1 mGy in the left retina (the more exposed organ) in 75% of single treatments and lower than 25 mGy in 95% of treatments. In the cases of 3 and 6 sessions, the left retina of 75% of patients absorbed respectively less than 36.3 and 72.7 mGy, whereas the left retina of 95% of patients received less than 75.2 and 150.4 mGy. Other organs were less exposed. Conclusion: This paper describes a method of absorbed dose estimation providing ranges used clinically in a single practice and the basis for further prospective studies. [ABSTRACT FROM AUTHOR]

Hand-foot syndrome (HFS) is a common skin toxicity of traditional chemotherapies. Some studies showed that HFS has an association with progression-free survival (PFS) and the overall survival (OS). So far, there is not available any systematic literature reviews or meta-analysis aimed to assess the associations between HFS, PFS and OS. For this reason, this study aims to quantitatively summarize, critically review, and interpret the recent literature related to the associations between HFS and efficacy of chemotherapy in terms of PFS and OS. Queries shaped by PICOM framework, a systematic search of three electronic databases (PubMed, Scopus, and Science Direct) was carried out for the period between January 2010 and December 2017. Quantitative data pooling was based on the calculation of Hazard Ratio (HR) with 95% Confidence Interval (95% CI) for the OS and PFS associated to the presence of HFS, through the data of original publications. Five papers were included in this systematic review for the quantitative data pooling. Patients with HFS showed improved PFS (HR = 0.532 [0.431-0.656]; p = 0.000) and improved OS (HR = 0.522 [0.427-0.638]; p = 0.000). HFS causes a reduction of compliance with oncology treatments. Healthcare providers should use this result as a trigger to foster patients' coping and the one of their family caregivers, enhancing their adherence to cancer treatments. [ABSTRACT FROM AUTHOR]

Ru(II) polypyridine complexes which can undergo photo-induced ligand dissociation and subsequent DNA covalent binding may potentially serve as photoactivated chemotherapeutic (PACT) agents. In this paper, three fluorinated dppz ligand coordinated Ru(II) complexes (2–4) containing four monodentate pyridine ligands were studied. All complexes released one pyridine and covalently bound to DNA upon 470 nm irradiation. Compared with the parent complex [Ru(dppz)(py)4]2+ (1), 2–4 displayed enhanced phototoxicity but diminished dark cytotoxicity, more favorable for PACT application. Complex 3 is the most efficient one with IC50 values of about 8 μM toward HeLa and SKOV-3 cell lines, and also has a much higher IC50 value toward normal L-02 cells. Our results indicate that fluorination on the retaining ligand may be an efficient way to improve the drug activity of Ru(II) PACT agents. [ABSTRACT FROM AUTHOR]

Review effectiveness of low-level laser therapy (LLLT) in the curative treatment of oral mucositis (OM) in patients receiving cancer therapy. A systematic review with meta-analysis was performed using Medline, Embase, and Cochrane Library databases according to PRISMA guidelines, to identify randomized controlled trials (RCT) on OM in patients during and/or after cancer therapy and in which the therapeutic approach was LLLT, with wavelengths between 632 and 970 nm. We considered grade of OM as a dichotomous variable (such as an improvement or not in severe OM on the seventh day of therapy), with the analysis of subgroups of adult patients or children and adolescents and as a continuous variable with determination of the time for the complete resolution and the subgroup analysis occurred with the strata of the samples by treatment only with chemotherapy or chemotherapy and radiotherapy. This paper's protocol was registered a priori at https://www.crd.york.ac.uk/PROSPERO . We found five RCT (total of 315 patients) with adequate methodology. LLLT was effective, presenting a 62% risk reduction of severe mucositis on the seventh day of evaluation (RR = 0.38 [95% CI, 0.19-0.75]). When we analyzed subgroups, RR was 0.28 (95% CI 0.17-0.46) in the adult studies and 0.90 (95% CI, 0.46-1.78) in the studies with children and adolescents. We demonstrated a mean reduction of 4.21 days in the time of complete resolution of OM (CI - 5.65 to - 2.76) in favor of LLLT. There is moderate evidence that LLLT is effective in resolving OM lesions in adult patients undergoing cancer therapy. LLLT demonstrates potential for decreasing the resolution time of OM lesions by approximately 4.21 days. [ABSTRACT FROM AUTHOR]

Objective: A systematic review and meta-analysis was conducted to investigate whether gonadotropin-releasing hormone analogs (GnRHa) have a protective role in women treated with alkylating agents. Data Sources: Major databases (PubMED, EMBASE, Cochrane Central Register of Controlled Trials), systematic snowballing, and trial registries were screened from the inception dates until September 2017. Methods and Study Selection: Comparative studies involving reproductive-aged women undergoing chemotherapy with or without coadministration of GnRHa were included. Spontaneous menstrual resumption was assessed as a main outcome. Statistical analyses were performed with STATA 14.2 statistical software. Effect estimates were presented as risk ratios (RR) with 95% confidence intervals (CIs). Results: The literature search yielded 25 436 citations and 84 papers were assessed in full text. Eighteen studies (11 randomized controlled trials [RCTs] and 7 cohort studies) published between 1987 and 2015 were included in the analysis, revealing a significant protective effect of GnRHa (n = 1043; RR:1.38; 95% CI: 1.18-1.63) although with high heterogeneity (I2 = 83.3%). Subgroup analyses revealed a significant benefit of GnRHa cotreatment both in RCTs and in cohort studies. Statistical significance was found in all subgroups by the underlying disease, that is, hematological malignancies, autoimmune diseases, and breast cancer. Sensitivity analyses in GnRH agonist-treated patients, in patients younger than 40 years old, and in patients without supradiaphragmatic radiotherapy also revealed a significant benefit of GnRHa cotreatment. Conclusion: Our results indicate that concurrent GnRHa administration is an effective method to decrease gonadotoxicity of alkylating agents. The presence of low-quality evidence favoring gonadoprotective effect requires a strong recommendation for offering GnRHa coadministration to young women who are to undergo gonadotoxic chemotherapy. Capsule: The present systematic review and meta-analysis shows a significant gonadoprotective effect of gonadotropin-releasing hormone analogs in women treated with alkylating agents. [ABSTRACT FROM AUTHOR]

Adipose tissue (AT) is an extramedullary reservoir of normal hematopoietic stem cells (HSCs). Adipocytes prevent the production of normal HSCs via secretion of inflammatory factors, and adipocyte-derived free fatty acids may contribute to the development and progression of leukemia via providing energy for leukemic cells. In addition, adipocytes are able to metabolize and inactivate therapeutic agents, reducing the concentrations of active drugs in adipocyte-rich microenvironments. The aim of this study was to detect the role of adipocytes in the progression and treatment of leukemia. Relevant literature was identified through a PubMed search (2000–2018) of English-language papers using the following terms: leukemia, adipocyte, leukemic stem cell, chemotherapy, and bone marrow. Findings suggest the striking interplay between leukemic cells and adipocytes to create a unique microenvironment supporting the metabolic demands and survival of leukemic cells. Based on these findings, targeting lipid metabolism of leukemic cells and adipocytes in combination with standard therapeutic agents might present novel treatment options. [ABSTRACT FROM AUTHOR]

Anthracyclines are highly effective chemotherapeutic agents, used for a wide variety of malignancies. Cardiotoxicity is a well-recognized side effect of anthracycline therapy that limits the total amount of drug administered and can cause heart failure in some patients. Most experimental data support oxidative stress as the etiology of anthracycline-induced cardiotoxicity. The objective of this paper was to provide a review of the clinical classification, risk factors, monitoring and prevention of anthracycline-induced cardiotoxicity in patients with breast cancer. [ABSTRACT FROM AUTHOR]

Introduction: Glioma and meningioma, the 2 most common primary tumours of the optic nerve and optic nerve sheath are usually benign, slow-growing tumours. The aim of the paper is to provide an overview of clinical, histological and radiological features of the most common primary tumours of the optic nerve and optic nerve sheath, as well as to discuss available treatment options. Materials and methods: A literature review was performed based on articles discussing optic nerve glioma and meningioma of the optic nerve sheath. Results: Glioma is the most common primary tumour of the optic nerve. In 90% of the patients, the onset is within the first 2 decades of life. Meningioma is the most common primary tumour of the optic nerve sheath. In 95% of the sufferers, the onset is in adulthood. Although rare in the general population, primary tumours of the optic nerve and its sheath are seen more often in patients with neurofibromatosis (NF). Glioma more often affect patients with NF1, whereas meningiomas more often affect those with NF2. Unlike in children, optic nerve glioma in adults can be malignant. On the other hand, optic nerve sheath meningioma tends to be more malignant in children rather than in adults. The symptoms of optic nerve glioma and optic nerve sheath meningioma can be similar, including vision impairment and proptosis. The diagnosis is based on orbital imaging with magnetic resonance image (MRI) or computed tomography (CT). The management most often involves clinical observation. Surgery, radiation therapy or chemotherapy are only used in selected cases with the risk of optic chiasm or fellow optic nerve involvement. Conclusions: Primary tumours of the optic nerve and optic nerve sheath are rare. Consolidated knowledge and improved understanding can aide early diagnosis and proper management of such cases. [ABSTRACT FROM AUTHOR]

Docetaxel, derived from the yew tree, belongs to the taxane family of medications. It works by disrupting the normal function of microtubules, thereby stopping cell division. Docetaxel is used in the treatment of ovarian, breast, esophageal, gastric, prostate, lung, and head and neck cancers. Common side effects include hair loss, low blood cell counts, peripheral neuropathy, vomiting, and muscle pain. Auricular chondritis with ear deformity has not been reported previously as a side effect of docetaxel. In this paper, we present the case of a 64-year-old male patient with chondritis accompanied by ear deformity that developed due to docetaxel–carboplatin chemotherapy for non-small cell lung cancer. [ABSTRACT FROM AUTHOR]

Cancer-related anemia (CRA) is a commonly occurring problem for patients with cancer regardless of whether they are receiving treatment with chemotherapy or immunotherapy. It may result from one or more processes (decreased production, increased destruction, or increased loss of red blood cells, RBC). Perturbations in iron availability form the primary basis for anemia in many patients with cancer-related anemia. Functional iron deficiency (FID) anemia is a condition in which the patient has adequate or increased iron stores, but this iron pool is not available for erythropoiesis. Erythropoiesis-stimulating agents (ESAs) were the original treatment for FID; over time, however, if the supply of iron cannot keep pace with increased RBC synthesis driven by ESAs, FID may eventually lead to the lack or loss of ESA responsiveness. Subsequent clinical trials reported that intravenous (IV) iron could enhance the erythropoietic response to ESAs. This chapter reviews the pathogenesis of FID and summarizes the literature on the treatment of cancer- and chemotherapy-induced anemia. Clinical trials using IV iron with or without ESAs are reviewed in addition to the currently available IV iron products. The consensus conclusions from these trials, as well as guideline recommendations, support the use of IV iron in these patients to enhance ESA responsiveness, decrease ESA dosage, and reduce RBC transfusions. Little data have been published on the long-term safety of IV iron or its impact on tumor growth. This paper also briefly explores novel approaches for the treatment of FID anemia, which has relevance in treating not only cancer patients but also patients with benign inflammatory disorders. [ABSTRACT FROM AUTHOR]

Introduction. Oncology nursing as a specialized field ought to develop a range of standards that will increase the quality of patient care. The indispensable ability of a nurse is to create patient-specific diagnoses that holistically describe the biopsychosocial status of the care focus. Aim. The proposal to use the ICNP® classification in the process of nursing a patient with malignant breast cancer during chemotherapy. Material and methods. The case study method was used in the paper. The research techniques used in the work include an interview, nursing observation, measurement, documentation analysis. The tools include a sheet for collecting patient data, the Acceptance of Illness Scale (AIS), Nutritional Risk Score questionnaire (NRS), scale of judgement of the occurrence of chemotherapy side effects, dyspnoea assessment, nausea assessment, fall rating as well as the Scale of nausea and vomiting judgement according to WHO criteria. Results. After the interview, the biopsychosocial status of the patient was assessed. Using the obtained empirical data, nursing diagnoses were made using the ICNP® reference terminology. The focus of care, nursing interventions, means / tools and the result of care were listed using phrases from the existing ICNP® catalogs. Conclusions. Using the International Classification of Nurses' Diagnosis ICNP® in the context of caring for a patient diagnosed with breast cancer allows to identify nursing problems such as: lymph edema, diarrhea, anxiety, exercise dyspnea, vomiting, concern about body image, risk of falling. [ABSTRACT FROM AUTHOR]

Background: Growing evidence has indicated that tumor biomarkers, including cytokeratin 19 fragment antigen 21-1 (Cyfra21-1), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 72-4 (CA72-4), carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC-Ag) were reported to be commonly used in diagnosis and prognosis in esophageal squamous cell carcinoma (ESCC). However, which is the best marker for predicting prognosis remains unknown. Few papers focused on the relationship between tumor biomarkers and postoperative treatment in ESCC.Methods: A total of 416 ESCC patients were enrolled in this study. The association between tumor markers and overall survival (OS) was analyzed using Kaplan-Meier method with log-rank test, followed by multivariate Cox regression models.Results: The results of Cox multivariate analysis indicated that among these tumor biomarkers, CA19-9 (≥ 37 vs. < 37) [hazard ratio (HR) = 2.130, 95% confidence interval (CI) = 1.138-3.986, p = 0.018] and CEA (≥ 5 vs. < 5) (HR = 1.827, 95% CI = 1.089-3.064, p = 0.022) were the independent prognostic factors of poor OS. For the ESCC patients with CA19-9 < 37, CEA < 5 or SCC-Ag < 1.5, the surgery plus postoperative chemotherapy group had a significantly longer OS than the surgery group alone (p < 0.05), but this significant difference of OS between these two groups cannot be found in patients with CA19-9 ≥ 37, CEA ≥ 5 or SCC-Ag ≥ 1.5 (p > 0.05).Conclusions: CEA and CA19-9 maybe are superior to other tumor biomarkers as prognostic indicators in ESCC. CA19-9, CEA, SCC-Ag may be useful in predicting the therapeutic effect of postoperative chemotherapy in ESCC. [ABSTRACT FROM AUTHOR]

The morbidity and mortality associated with bacterial infections have remained significant despite chemotherapeutic advances. With the emergence of drug-resistant bacterial strains, the situation has become a serious threat to the public health. Thus, there is an urgent need to identify novel antibacterials. The majority of antibiotics available in the market are produced by bacteria isolated from soil. However, the low-hanging fruit has been picked; hence, there is a need to mine bacteria from unusual sources. With this in mind, it is important to note that animals and pests such as cockroaches, snake, crocodiles, and water monitor lizard come across pathogenic bacteria regularly, yet flourish in contaminated environments. These species must have developed methods to defend themselves to counter pathogens. Although the immune system is known to possess antiinfective properties, gut bacteria of animals/pests may also offer a potential source of novel antibacterial agents, and it is the subject of this study. This paper discusses our current knowledge of bacteria isolated from land and marine animals with antibacterial properties and to propose untapped sources for the isolation of bacteria to mine potentially novel antibiotic molecules. [ABSTRACT FROM AUTHOR]

Aims: Tumour deposits (TDs) are clusters of cancer cells in the soft tissue that are discontinuous from the primary tumour. In this review we are exploring their relevance for prognosis in patients with gastric cancer. Methods and results: A literature search was performed to identify studies providing data on TDs and prognosis in gastric cancer patients. Eight papers were included in the meta‐analysis, which was carried out in terms of risk ratios (RR) and hazard ratios (HR) with 95% confidence interval (95% CI). Of 7445 patients, 1551 had TDs (20.9%). TDs were associated with a decreased overall survival (OS) in univariate (HR = 2.82, 95% CI = 1.9–4.3) and multivariate analyses (HR = 1.65, 95% CI = 1.3–2.1). TDs were also associated with known prognostic factors such as synchronous metastatic disease (RR = 9.5), invasion depth (RR = 1.8), lymph node metastasis (RR = 1.7), lymphatic invasion (RR = 1.7), vascular invasion (RR = 2.6) and poor differentiation (RR = 1.2). Conclusions: We found a strong indication that TDs are independent predictors of prognosis in patients with gastric cancer; hence, TDs should be included in the staging of gastric cancers. [ABSTRACT FROM AUTHOR]

We consider a state-constrained optimal control problem of a system of two non-local partial differential equations, which is an extension of the one introduced in a previous work in mathematical oncology. The aim is to control the tumor size through chemotherapy while avoiding the emergence of resistance to the drugs. The numerical approach to solve the problem was the combination of direct methods and continuation on discretization parameters, which happen to be insufficient for the more complicated model, where diffusion is added to account for mutations. In the present paper, we propose an approach relying on changing the problem so that it can theoretically be solved thanks to a Pontryagin's maximum principle in infinite dimension. This provides an excellent starting point for a much more reliable and efficient algorithm combining direct methods and continuations. The global idea is new and can be thought of as an alternative to other numerical optimal control techniques. [ABSTRACT FROM AUTHOR]

In this paper, a non-trivial generalization of a mathematical model put forward in [35] to account for the development of resistance by tumors to chemotherapy is presented. A study of the existence and local stability of the solutions, as well as the ultimate dynamics of the model, is addressed. An analysis of different chemotherapeutical protocols using discretization and optimization methods is carried out. A number of objective functionals are considered and the necessary optimality conditions are provided. Since the control variable appears linearly in the associated problem, optimal controls are concatenations of bang-bang and singular arcs. A formula of the singular control in terms of state and adjoint variables is derived analytically. Bang-bang and singular controls from the numerical simulations are obtained where, in particular, singular controls illustrate the metronomic chemotherapy. [ABSTRACT FROM AUTHOR]

We analyze mathematical models for cancer chemotherapy under tumor heterogeneity as optimal control problems. Tumor heterogeneity is incorporated into the model through a potentially large number of states which represent sub-populations of tumor cells with different chemotherapeutic sensitivities. In this paper, a Michaelis-Menten type functional form is used to model the pharmacodynamic effects of the drug concentrations. In the objective, a weighted average of the tumor volume and the total amounts of drugs administered (taken as an indirect measurement for the side effects) is minimized. Mathematically, incorporating a Michaelis-Menten form creates a nonlinear structure in the controls with partial convexity properties in the Hamiltonian function for the optimal control problem. As a result, optimal controls are continuous and this fact can be utilized to set up an efficient numerical computation of extremals. Second order Jacobi type necessary and sufficient conditions for optimality are formulated that allow to verify the strong local optimality of numerically computed extremal controlled trajectories. Examples which illustrate the cases of both strong locally optimal and non-optimal extremals are given. [ABSTRACT FROM AUTHOR]

Abstract Morpholine, a six-membered heterocycle containing one nitrogen and one oxygen atom, is a moiety of great significance. It forms an important intermediate in many industrial and organic syntheses. Morpholine containing drugs are of high therapeutic value. Its wide array of pharmacological activity includes anti-diabetic, anti-emetic, growth stimulant, anti-depressant, bronchodilator and anticancer. Multi-drug resistance in cancer cases have emerged in the last few years and have led to the failure of many chemotherapeutic drugs. Newer treatment methods and drugs are being developed to overcome this problem. Target based drug discovery is an effective method to develop novel anticancer drugs. To develop newer drugs, previously reported work needs to be studied. Keeping this in mind, last five year's literature on morpholine used as anticancer agents has been reviewed and summarized in the paper herein. Graphical abstract Image 1 Highlights • Present review highlights the use of morpholine as a privileged scaffold in the synthesis of anti-cancer agents. • Morpholine as anti-cancer drug acting through various targets has been summarized. • SAR studies of the previously synthesized morpholine compounds have been briefly discussed. • Present review may be helpful for designing new morpholine containing anti-cancer drugs with better work profile. [ABSTRACT FROM AUTHOR]