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Objectives To evaluate the association and risk factors of healthcare-associated infection (HAI) and burden of illness among chemotherapy-induced ulcerative mucositis (UM) patients. Methods For this research, US National Inpatient Sample database 2017 was utilized to study UM patients. The association of healthcare-associated infection-related burden of illness among UM patients was assessed on the outcome––length of hospital stays (LOS), total charges, in-hospital mortality, and discharge disposition. Result In 2017, there were 11,350 adult (> 18 years of age) UM patients, among them there were 415 (3.5%) HAI. After adjusting for patient and clinical characteristics, UM patients with HAI were most likely to have higher total charges and longer LOS (1.91; 95% CIs: 1.51–2.41; P

Rationale: Leukoencephalopathy, a complication associated with chemotherapy has been reported after giving high doses of methotrexate and cytarabine with no specific risk factors to date. Objectives: To review the prevalence of chemotherapy-induced leukoencephalopathy in children with acute lymphoblastic leukemia (ALL). To present the clinical course, pathogenesis and neuro-imaging findings of chemotherapy-induced leukoencephalopathy in children with ALL. Case: We reported three cases of adolescent ALL precursor B-cell patients who received high doses of methotrexate and presented with neurologic and MRI findings consistent with leukoencephalopathy. Our patients were only placed on supportive measures with adequate hydration, without providing any special intervention. Yet, all of them had complete neurological recovery. Discussion and Summary: Methotrexate is a cell cycle-specific agent that inhibits the enzyme dihydrofolate reductase, preventing the conversion of folic acid to tetrahydrofolic acid and inhibiting cell replication. It is one of the most commonly implicated drug causing leukoencephalopathy.[3] On MRI T2-weighted images, all of them had hyperintensities on the posterior frontal/parietal corona radiata and centrum semiovale consistent with leukoencephalopathy. Complete recovery happened spontaneously in all of the cases. There is no standard treatment for acute and subacute toxicities from methotrexate. Keywords: Leukoencephalopathy, Chemotherapeutic drugs, Neurotoxicity, Case series

Background: Paclitaxel-induced painful neuropathy is a major dose-limiting side effect and can persist for up to two years after completing treatment that greatly affects both the course of chemotherapy and quality of life in cancer patients. Peroxisome proliferator-activated receptor (PPAR)-γ belongs to a family of nuclear receptors known for their transcriptional and regulatory roles in metabolism, inflammation, and oxidative stress. However, the role of PPAR-γ activation on paclitaxel-induced neuropathic pain is not yet known. Objective: To investigate whether pioglitazone, a PPAR-γ agonist reduce paclitaxel-induced neuropathic pain and to elucidate underlying mechanisms. Methodology: Peripheral neuropathy was induced by administration of paclitaxel (2 mg/kg per injection) intraperitoneally on four alternate days (days 0, 2, 4, 6). Thermal hyperalgesia and mechanical allodynia were assessed and the markers of inflammation and nitroso-oxidative stress were estimated. Results: Pioglitazone did not induce hypoalgesia and had no effect on locomotor activity. Repeated oral administration of pioglitazone (10 and 20 mg/kg,) for 2 weeks started 14 days after paclitaxel injection markedly attenuated paw withdrawal responses to thermal (hyperalgesia) and mechanical (allodynia) stimuli. Further, pioglitazone administration significantly reduced elevated level of pro-inflammatory cytokine, TNF-α, in both the dorsal root ganglia and the spinal cord accompanied by marked decrease in oxidative stress parameters as well as increase in activity of antioxidant defense enzyme, superoxide dismutase, in the spinal cord after paclitaxel injection. Conclusion: The results of the present study demonstrate that pioglitazone, a PPAR-γ agonist exerted antinociceptive effect in paclitaxel-induced neuropathic pain through inhibiting neuroimmune inflammation in both the periphery and spinal cord and by reducing nitroso-oxidative stress in spinal cord. Our findings strongly suggest pharmacological activation of PPAR-g as a promising therapeutic target in paclitaxel-induced peripheral neuropathy and provide rationale for the clinical evaluation.

Objectives: Hand-foot syndrome (HFS) is a common adverse effect of chemotherapy in cancer patients. This review synthesizes research results to assess the effect of traditional Korean medicine (TKM) on HFS in cancer patients.Methods: Four databases (PubMed, The Cochrane Central Register of Controlled Trials, Research Information Sharing Service, China National Knowledge Infrastructure) were searched for randomized controlled trials (RCTs) to assess the effects of TKM on HFS. The effects and quality of RCTs were assessed with the Cochrane risk of bias (ROB) tool.Results: Six RCTs met our study criteria. In all six, TKM showed improvement in HFS symptoms as well as quality of life scores when compared to the control group. However, the methodological quality of RCTs was relatively low due to the unclear or high ROB.Conclusions: TKM would be helpful to patients with HFS after chemotherapy. To clarify the clinical efficacy of TKM, well-designed studies are required in the future.

Background Chemotherapy-induced cognitive impairment (CICI) is a debilitating side effect arising from chemotherapy treatments. The condition is characterised by a range of cognitive deficits including impairment to memory, attention, and concentration. Whilst the underlying mechanisms that contribute to CICI remain unclear, neuroinflammation has been suggested as one key contributor. Method A comprehensive systematic search of EMBASE and Medline via PubMed was conducted to identify studies on neuroimmune reactivity marker expression changes and resulting cognitive changes in preclinical rodent models of CICI. Results A total of twenty studies met the eligibility criteria and were included in the scoping review. There was significant heterogeneity in the methodology employed in the included studies. Our findings demonstrate that widespread changes in cytokines, chemokines, microglia reactivity, and astrocyte reactivity are observed in CICI in the brain regions expected to be affected, given the nature of the cognitive impairment observed in CICI. Conclusions Although there was considerable heterogeneity in study design that made comparisons between studies difficult, our findings suggest that neuroinflammation commonly occurs in CICI preclinical rodent models and shows an association with cognitive impairment.

Diabetic neuropathy and chemotherapy-induced peripheral neuropathy are complex disorders affecting different nerve fiber group and remain as major source of morbidity and decreased quality of life of the patients. Given the recent advance in understanding the pathophysiological mechanism of these neuropathies and the development of new drugs, it is imperative to set proper scales to rate the severity of symptoms or signs. Moreover, well-designed, highly sensitive and valid scales could get scientific reliability and clinical utility if they are combined with objective neurophysiological measures. This review will discuss about the reliable and validated scales used in these common toxic and metabolic neuropathies.

Patients with cancer undergoing chemotherapy are at risk of thrombocytopenia. The co-incidence of cancer-associated venous thromboembolism (VTE) and thrombocytopenia is a frequent complication in patients with cancer. Especially in certain tumour entities at high VTE risk, chemotherapeutic agents with myelosuppressive effects are part of the standard of care. The management of cancer-associated VTE in the setting of chemotherapy-induced thrombocytopenia is challenging, in the absence of evidence from high-quality studies. Thrombocytopenia is associated with both increased risk of recurrent VTE and risk of bleeding during anticoagulation. In this case-based concise review, we aimed at summarizing available literature and expert consensus guidance on the treatment of cancer-associated VTE in patients with chemotherapy-induced thrombocytopenia.

Aim The aim of this study was to assess the effectiveness of listening to music or Quran in reducing cancer patients’ anxiety before chemotherapy administration. Reducing anxiety in people with cancer, prior to chemotherapy administration, is a crucial goal in nursing care. Design An experimental comparative study was conducted. Methods A simple randomization sampling method was applied. Two hundred thirty‐eight people with cancer who underwent chemotherapy were participated. They are assigned as Quran, music and control groups. Results The overall score of Arabic State Anxiety Inventory in all groups revealed that there was a significant difference between pre‐test and post‐test among participants. Listening to Quran or music reduced the chemotherapy‐induced anxiety. There was no difference between these two ways to reduce anxiety in people with cancer. Listening to Quran or music can be added in nursing care plans prior chemotherapy administrations to reduce cancer patients’ anxiety.

Introduction: Peg and other G-CSFs are widely used in BC patients receiving myelosuppressive chemotherapy. We previously reported that Peg’s mechanism of action (MoA) for CIN -prevention protects in week 2 of the cycle. BC pts receiving Doc/Doxorubicin/Cyclophosphamide (TAC) are unprotected in week 1. [Study BPI-2358-106 (NCT03102606) Blayney, St Gallen 2019]. In this study, the novel CIN agent Plinabulin (Plin), with a MoA different, yet complimentary to Peg CIN, prevented severe CIN in week 1 of the Cycle (C), and given in combination with Pegflgrastim, offered superior protection throughout the entire cycle. Other Study 106 results indicated that monotherapy Peg is a sub-optimal CIN prophylaxis strategy in TAC-treated BC pts. In Study BPI-2358-105 (NCT03102606) we evaluated Peg monotherapy as CIN preventive therapy in BC pts. Methods: In Study 105, BC, lung (NSCLC) and prostate cancer (HRPC) pts with at least 1 risk factor as per NCCN guidelines, received Doc 75 mg/m2 with either Peg 6mg (n=53) or Plin 40 mg (n=52), and had frequent blood draws in C1 for Neutrophil count assessment. Grade (Gr) 4 Neutropenia (N) frequency in C1, Duration of Severe Neutropenia (DSN) in C1, and frequency of clinical sequelae of N (Hospitalizations, Infections, FN, antibiotic use, chemotherapy dose reductions) in C1 to C4 were calculated in BC (n=27) and NSCLC/HRPC (n=26) pts receiving Doc 75 mg/m2. There were 9 pts in the HRPC group in the Peg arm. Results:No HRPC and 4% (1pt) NSCLC pts of peg-treated developed Gr 4 N, whereas 16% of Peg-treated BC pts developed Gr 4 N. Gr 4 N frequency over time in C1 was significantly higher in BC pts vs NSCLC/HRPC pts (p5 times longer (p Conclusions: In BC pts treated with Peg monotherapy after Doc 75 mg/m2, Peg is significantly less effective for CIN prevention compared to NSCLC/HRPC pts. The sub-optimal efficacy of Peg was due to its protection occurring in week 2 of the Cycle, leaving a significant number of pts unprotected in week 1 of the Cycle. The demonstrated effectiveness of Plinabulin in week 1 of the Cycle in BC pts, when combined with Peg could offer superior CIN protection vs Peg alone in BC pts receiving Doc. Gr4N %BaselineC1D1C1D2C1D6*C1D7C1D8C1D9C1D10C1D15BC0%0%0%16%12%4%4%4%0%NSCLC/ HRPC0%0%0%4%4%0%0%0%0%*On C1D6, Gr 4 frequency in the Plin arm was 0% in BC pts Citation Format: Douglas W. Blayney, Greg Ginn, Lan Huang, Ramon Mohanlal. Differential efficacy of pegfilgrastim (Peg) in patients (pts) with breast cancer (BC) versus other cancer types for the prevention of docetaxel (Doc) chemotherapy-induced neutropenia (CIN) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-34.

Purpose: To evaluate mental health, cognitive function, and living quality of colon and rectal carcinoma patients with oxaliplatin-induced neurotoxicity. Methods: Fifty recurrence-free colorectal cancer (CRC) patients with oxaliplatin chemotherapy while 50 control patients without oxaliplatin chemotherapy were enrolled in this study. Subjective and objective aspects of oxaliplatin chemotherapy symptoms were assessed with oxaliplatin neurotoxicity classification. Psychological assessment was measured via the Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS). Cognitive function was measured via Montreal Cognitive Assessment (MoCA). Quality of Life (QOL) was assessed using the World Health Organization’s Quality of Life (WHOQOL-BREF) shortened instrument. Results: Of the patients with oxaliplatin chemotherapy, 41 patients had depression and 42 patients had anxiety. Patients with oxaliplatin chemotherapy scored higher on average on both the SDS (64.36 ± 7.22) and SAS (67.49 ± 9.41) compared to those without oxaliplatin chemotherapy (SDS, 57.86 ± 5.27, p=0.006; SAS, 61.57 ± 10.06, p = 0.004). Patients with oxaliplatin chemotherapy, on average, scored lower on the MoCA (23.46 ± 3.17) compared to patients without oxaliplatin chemotherapy (27.49 ± 2.03, p < 0.05). In addition, patients with oxaliplatin chemotherapy scored significantly lower on measures of physical health (18.9 ± 7.8 vs. 37.8 ± 6.2, p

Objective To evaluate the protective role of L-Arginine in cisplatin induced acute renal injury through assessment of renal, oxidative stress and inflammatory markers in albino wistar rats. Methods: Quasi-experimental study was conducted at the department of physiology and postgraduate research laboratory at Isra University, Hyderabad, Sindh from April 2019 to September 2019. Thirty male Albino wistar rats were selected through non-random purposive sampling and divided equally into three different groups: Group-A (Control group), Group-B (experimental group) received Cisplatin alone and Group-C (experimental group) received Cisplatin along with arginine. After sacrificing the animals, blood samples were collected through cardiac puncture while renal histopathological analysis was under the light microscope. The changes in severity were observed using a graded scale. Data was analysed using SPSS v23.0. Results: There was a statistically significant (p-value

Oral mucositis is a distressing complication of chemotherapy-induced toxicity in cancer patients, it effect on the well-being of patients, demonstrating its negative impact on patients’ quality of life, and may lead to dose reduction among patients. Hence, the present study was conducted to evaluate the effect of educational guidelines on reducing chemotherapy induced oral mucositis based on patients' needs assessment. A quasi-experimental research design (pretest and posttest) has been conducted to achieve the aim of this study. This study was conducted in the inpatients' department at Radiotherapy and Nuclear Medicine Department, affiliated to Ain Shams University. A purposive sample of 70 adult patients was selected based on certain inclusion criteria. A structured interview questionnaire, Oral assessment guide, and Patients' health condition assessment (Patient-related outcomes PROMs) are methods used to collect the data among the studied patients. There was statistically significant improvement in the post-test implementation of educational guidelines as regard patient's mouth care practice with p-value

Breast cancer is the most commonly occurring neoplasm in women, which can be curable as well as can reduce the recurrence of cancer, with the help of various multidisciplinary approaches and thereby decrease the morbidity as well as mortality. Chemotherapy is a well-defined therapeutic approach for breast cancer, but cardiotoxicity is the most potential side-effect associated with chemotherapeutic drugs. Doxorubicin, along with cyclophosphamide, produces serious cardiotoxicity due to potential drug interaction. It is a case of a 63-year-old female patient post-menopausal with k/c/o type 2 diabetic Mellitus on medication. Clinically and radiologically, she was diagnosed with carcinoma left breast (IMC grade III, TNBC, CT2N0Mx). She underwent breast-conserving surgery (BCS) or lumpectomy without reconstruction. The HPE report suggestive of infiltrating mammary carcinoma NST grade 3. She was currently on adjuvant chemotherapy IInd cycle. Post chemotherapy, she was admitted with complaints of chest discomfort and chest pain. Screening ECHO showed grade I diastolic dysfunction and also the cardiac enzymes and cardiac marker troponins I was found to be elevated. She had undergone CAG for risk stratification. She was thought to have chemotherapy-induced cardiotoxicity associated with atypical chest pain and was advised medical follow up. Doxorubicin and cyclophosphamide-induced cardiac dysfunction and associated adverse events can be prevented or minimized with dose modification, use of cardioprotective drugs, identifying patient-related risk factors and regular cardiac monitoring of the patient receiving chemotherapy with doxorubicin and cyclophosphamide in breast cancer treatment.

Background: Of the many side effects suffered by cancer patients, those related to cognitive performance have become increasingly prominent in clinical practice. We know that chemotherapy generates a series of side effects, such as nausea and vomiting, alopecia, and so on, which can be counteracted by complementary medication. However, in the case of post-chemotherapy cognitive impairment, or chemo brain, these cannot be controlled with drug therapies. However, before any intervention can be considered, it is necessary to know exactly what cognitive impairment is being triggered. For this reason, we decided to study the cognitive status of breast cancer patients. Methods: analytical, prospective, three-measure longitudinal, intrasubject unifactorial, non-probabilistic and accidental assignment study. The sample came from the Medical Oncology Department at Hospital de Salamanca, in Spain. Cognitive function (Trail Making Test and Stroop Test) was established as the primary variable; the presence of sleep disorders (Insomnia Severity Index, ISI) and anaemia (haemoglobin levels in blood) were analysed as secondary variables, in addition to sociodemographic variables (age, stage, type of carcinoma, radiotherapy, menopause, social support network, marital status, years of schooling and employment status). Results: We recruited 151 individuals according to the selection criteria. We can confirm that factors including anaemia, menopause, patient support network and marital status, years of schooling, and employment status did affect the cognitive performance of the patients in active chemotherapy treatment in the study. In contrast, sleep disorders, age, radiotherapy treatment, stage of disease, and type of carcinoma did not affect the cognitive performance of the cancer patients. Conclusions: Chemotherapy does impact the cognitive performance of breast cancer patients.

Prevention of left ventricular dysfunction predominantly induced by anthracyclines and/or trastuzumab still represents a challenge for cardio-oncology today. Indeed, this complication threatens to limit the significant gain in cancer survival achieved to date. Oncology strategies with cumulative dose limitation, continuous infusion, dexrazoxane, and liposomal formulations have been shown to decrease the risk of anthracycline cardiotoxicity. The preventive use of ace inhibitors, sartans, and/or beta-blockers has not yet provided convincing evidence and the positive effect on left ventricular ejection fraction decline appears poor without a clear clinical relevance. Assessment of the cardiovascular risk profile is a key aspect of the baseline evaluation of any patient scheduled for cancer therapy. Control and/or correction of modifiable cardiovascular risk factors is the first form of primary prevention of cardiotoxicity. It will be necessary to select populations at higher risk of developing cardiac dysfunction, identify patients genetically predisposed to develop cardiotoxicity in order to build the most appropriate strategies to correctly and timely target cardioprotective therapies.

Neutropenia is a common complication of chemotherapy in leukemic patients. An herbal formulation of chamomile was hypothesized to be effective on neutropenia. A group of healthy volunteers and two groups of patients received chamomile oral drop to be compared with a control group of neutropenic patients. Results showed an increase of white blood cells and resolution of neutropenia in all groups except for the control group. In conclusion, chamomile could be used as an effective complementary medicine for increasing the immunity of neutropenic patients (in addition to healthy individuals). Keywords: Chamomile; Leukemia; Chemotherapy; Neutropenia; Integrative Medicine; Persian Medicine

Introduction: Oral mucositis (OM) has been considered one of the most feared collateral effects of oncological treatments. Some therapies have been used, such as light-emitting diode (LED), with promising results, but with no sufficient evidence in the literature. Objective: Our study aimed to evaluate, by clinical and histological analysis, the effect of LED on the treatment of chemotherapy-induced OM (CIOM) in an animal model. Methods: Twenty male hamsters were equally distributed to two groups: control (C), which received anesthesia and CIOM induction; and LED (L), which received anesthesia, CIOM induction, and LED treatment (635 nm, 120 mW, 0.48 J). The clinical analysis was performed through two specific scales for OM analysis on days 5, 7 and 10 of the experiment. In addition, the injured area of all hamsters check pouch mucosa was removed and processed for histological analysis on the last experimental day. Results: After statistical analysis, group L showed less severity of OM when compared with the C group (P

Acute lymphocytic leukemia (ALL) is one of the most common malignancies, especially in young people. Combination chemotherapy for ALL typically includes corticosteroids (Kantarjian et al., 2000). Hyperglycemia is a well-recognized complication of corticosteroids, and chemotherapy-induced diabetes (CID) is not uncommon (27.5%–37.0%) during the treatment of ALL (Hsu et al., 2002; Weiser et al., 2004; Alves et al., 2007). Besides the effect of corticosteroids, potential factors triggering hyperglycemia in ALL also include direct infiltration of the pancreas by leukemia cells and β cell dysfunction induced by chemotherapeutic agents such as L-asparagine (Mohn et al., 2004).

Amaç: Siklofosfamid (CP), hepatotoksisite dahil olmak üzere, toksik yan etkilerine rağmen yaygın olarak kullanılan kemoterapötik bir ajandır. Ellajik asit (EA) antioksidan bir ajandır ve serbest radikal süpürücü aktiviteler sergilemektedir. Bu deneysel çalışmada, EA'nın, CP'ye bağlı karaciğer hasarı üzerindeki etkileri araştırılmıştır.Gereç ve Yöntemler: Yirmi dört adet Sprague-Dawley türü sıçan (180-220 gr) dört eşit gruba ayrıldı. Hepatotoksisite oluşturmak için intraperitonal olarak tek doz 150 mg/kg CP verildi. CP uygulamasından 20 dakika önce ve 4 ila 8 saat sonra oral yolla farklı dozlarda (50 ve 75 mg/kg) EA uygulandı. Serumun biyokimyasal analizlerinin yanı sıra böbrek dokularının histopatolojik değerlendirmesi ve kaspaz-3 için immünohistokimyasal değerlendirme yapıldı.Bulgular: CP uygulanan grup, kontrol grubuna kıyasla, serum hepatik enzimleri olan aspartat aminotransferaz (AST) ve alanin aminotransferaz (ALT)’da önemli bir artış gösterdi. Benzer şekilde, total trigliserit (TG) ve çok düşük yoğunluklu lipoprotein kolesterol (VLDL-C) seviyeleri önemli ölçüde arttı. Ayrıca, yüksek yoğunluklu lipoprotein kolesterol (HDL-C) seviyeleri, kontrol grubuna kıyasla anlamsız olarak azaldı. Her iki EA dozunda da VLDL-C, AST, ALT seviyeleri önemli ölçüde azalırken, HDL-C seviyesi önemli bir artış gösterdi. 75 mg/kg EA tedavisi, total kolesterol (TC) konsantrasyonunda önemsiz bir artışa neden oldu. CP uygulanan grubun karaciğerlerinde mikroskobik olarak önemli derecede konjesyon, ödem, dejenerasyon ve nekroz gözlendi. Bununla beraber EA-75 grubundaki hayvanlarda ödem, dejenerasyon ve nekroz önemli ölçüde azaldı. Ayrıca kaspaz-3 ekspresyonu EA-75 grubunda anlamlı şekilde azaldı.Sonuç: Bu sonuçlar sıçanlarda CP'nin neden olduğu hepatotoksisitede EA'nın koruyucu etkisi olduğunu göstermiştir., Aim: Cyclophosphamide (CP) is a commonly used chemotherapeutic agent despite its toxic adverse effects, including hepatotoxicity. Ellagic acid (EA) is an antioxidant agent and exhibits free radical scavenging activities. In this experimental study, the effects of EA on CP-induced liver injury were investigated.Material and Methods: Twenty-four Sprague-Dawley rats (180-220 gr) were separated into four equal groups. A single dose of 150 mg/kg CP was given intraperitoneally to generate hepatotoxicity. Different doses (50 and 75 mg/kg) of EA were administered orally 20 minutes before, 4 and 8 hours after CP administration. The histopathological evaluation of kidney tissues and immunohistochemical evaluation for caspase-3 were conducted as well as the serum biochemical analyses.Results: CP treated group exhibited a significant increase in serum hepatic enzymes, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), compared to the control group. Similarly, the total triglycerides (TG) and very-low-density lipoprotein cholesterol (VLDL-C) levels increased significantly. Additionally, the high-density lipoprotein cholesterol (HDL-C) levels decreased, which was not significant, compared to the control group. At both EA doses, VLDL-C, AST, ALT levels decreased significantly while HDL-C level revealed a significant increase. 75 mg/kg EA treatment caused a non-significant elevation in total cholesterol (TC) concentration. Microscopic analysis showed a significant congestion, edema, degeneration and necrosis in the livers of CP administered group. However, edema, degeneration, and necrosis were significantly reduced in animals treated with EA-75. In addition, caspase-3 expression significantly decreased in EA-75 group.Conclusion: These results indicate the protective effects of EA in CP-induced hepatotoxicity in rats.

Background: While vomiting is well controlled with current antiemetic regimens, unrelieved chemotherapy-induced nausea (CIN) is a significant clinical problem. Perturbations in endocytotic and apoptotic pathways in the gut can influence the functioning of the microbiome-gut-brain-axis and the occurrence of gastrointestinal (GI) symptoms. However, limited information is available on the mechanisms that underlie unrelieved CIN. Objectives: The purpose of this study was to evaluate for perturbed biological pathways associated with endocytosis and apoptosis in oncology patients who did (n = 353) and did not (n = 275) report CIN prior to their second or third cycle of chemotherapy (CTX). Methods: Oncology patients (n = 735) completed study questionnaires in the week prior to their second or third cycle of CTX. CIN occurrence was evaluated using the Memorial Symptom Assessment Scale. Pathway impact analyses (PIA) were performed in 2 independent samples using RNA-sequencing (sample 1, n = 334) and microarray (sample 2, n = 294) methodologies. Fisher’s combined probability method was used to identify signaling pathways related to endocytotic and apoptotic mechanisms that were significantly perturbed between the 2 nausea groups across both samples. Results: CIN was reported by 63.6% of the patients in sample 1 and 48.9% of the patients in sample 2. Across the 2 samples, PIA identified 4 perturbed pathways that are involved in endocytosis (i.e., endocytosis, regulation of actin cytoskeleton) and apoptosis (i.e., apoptosis, PI3K/Akt signaling). Conclusions: Our findings suggest that CTX-induced inflammation of the GI mucosa, that results in the initiation of endocytotic and apoptotic processes in the gut, is associated with the occurrence of CIN.

PURPOSE To identify factors associated with chemotherapy-induced vomiting (CIV) control in pediatric patients receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC). MATERIALS AND METHODS An individual, patient‐level, pooled analysis was performed using data from five clinical trials of aprepitant or fosaprepitant in pediatric patients receiving HEC or MEC. The proportion of individuals who experienced no vomiting (complete CIV control) during the phase of interest was the primary study end point. The association of acute-phase complete CIV control (from first chemotherapy dose to 24 hours after the last chemotherapy dose of the chemotherapy block) with age, sex, race, cancer type, acute-phase duration, and antiemetic regimen was examined. Association of the same factors and acute-phase complete CIV control with complete CIV control in the delayed phase (end of acute phase until ≤ 96 hours later) was examined. RESULTS A total of 735 patients (mean age, 8.9 years; range, 0.3 to 17.9 years) were included in the acute-phase analysis. Acute-phase complete CIV control was less likely in older patients (relative risk [RR], 0.97 per year; 95% CI, 0.96 to 0.98 per year) and longer acute-phase duration (RR, 0.89 per day; 95% CI, 0.84 to 0.94 per day). Receipt of ondansetron plus aprepitant or fosaprepitant was associated with a higher likelihood of acute-phase complete CIV control versus ondansetron alone (RR, 1.28; 95% CI, 1.09 to 1.50). Delayed-phase complete CIV control was more likely in patients with acute-phase complete CIV control (RR, 1.19; 95% CI, 1.06 to 1.34) and in those who received aprepitant or fosaprepitant. CONCLUSION Younger age, shorter acute-phase duration, and antiemetic regimen were associated with acute-phase complete CIV control in pediatric patients receiving HEC or MEC. Acute-phase complete CIV control and antiemetic regimen were associated with delayed-phase complete CIV control.

Chemotherapy‐induced diarrhoea (CID) is a frequent chemotherapy adverse event in dogs. Yet, there is currently no consensus regarding its management. Smectite is a natural medical clay, widely used in the treatment of acute diarrhoea in humans. The objectives of this study were to assess the efficacy of smectite in the management of CID in dogs, and to collect epidemiological data on CID. For each episode of diarrhoea, dogs were randomized into two management groups: Smectite group, receiving smectite at 0.5 g/kg PO per day divided in two to three doses initiated at the start of CID; control group, without initial medication. In both groups, rescue metronidazole was prescribed if CID progressed or was not improved within 48 hours. Sixty dogs were recruited and received 426 chemotherapy administrations between June 2017 and March 2019. The incidence rate of CID was 110/426 (25.8%, 95% CI: 21.7%‐30.2%), and significantly differed between the chemotherapeutic drugs administered (P P P

For the constellation of neurologic disorders known as chemotherapy-induced peripheral neuropathy, mechanistic understanding and treatment remain deficient. Here, we present the first evidence that chronic sensory neuropathy depends on nonlinear interactions between cancer and chemotherapy. Global transcriptional profiling of dorsal root ganglia revealed differential expression, notably in regulators of neuronal excitability, metabolism, and inflammatory responses, all of which were unpredictable from effects observed with either chemotherapy or cancer alone. Systemic interactions between cancer and chemotherapy also determined the extent of deficits in sensory encoding and ion channel protein expression by single mechanosensory neurons, with the potassium ion channel Kv3.3 emerging as one potential contributor to sensory neuron dysfunction. Validated measures of sensorimotor behavior in awake, behaving animals revealed dysfunction after chronic chemotherapy treatment was exacerbated by cancer. Notably, errors in precise forelimb placement emerged as a novel behavioral deficit unpredicted by our previous study of chemotherapy alone. These original findings identify novel contributors to peripheral neuropathy and emphasize the fundamental dependence of neuropathy on the systemic interaction between chemotherapy and cancer. Significance: These findings highlight the need to account for pathobiological interactions between cancer and chemotherapy as a major contributor to neuropathy and will have significant and immediate impact on future investigations in this field.

PURPOSE OF REVIEW: There is a growing number of studies implicating gut dysbiosis in mucositis development. However, few studies have shed light on the causal relationship limiting translational potential. Here, we detail the key supportive evidence for microbial involvement, candidate mechanisms by which the microbiome may contribute to mucositis and emerging approaches to model host-microbe interactions with clinical relevance and translational potential.RECENT FINDINGS: Synthesis of existing clinical data demonstrate that modulating the microbiome drastically alters the development and severity of mucositis, providing a strong rationale for its involvement. Review of the literature revealed potential microbiome-dependent mechanisms of mucosal injury including altered drug metabolism, bile acid synthesis and regulation of the intestinal barrier. Current studies are limited in their mechanistic insight due to cross-sectional and would benefit from longitudinal analyses and baseline phenotyping.SUMMARY: The causative role of the microbiome in mucositis development remains unclear. Future studies must adopt comprehensive microbial analyses with functional assessment, and utilize emerging ex-vivo models to interrogate host-microbe interactions in mucositis.

Background: Protroca evaluated the efficacy and safety of primary and secondary prophylaxis of neutropenia with lipegfilgrastim (Lonquex®) in breast cancer patients receiving neoadjuvant or adjuvant chemotherapy (CT). Patients and Methods: Of the 255 patients enrolled, 248 patients were evaluable for the intent-to-treat (ITT) and 194 patients for the per-protocol set. Primary and secondary end points after lipegfilgrastim treatment were assessed. Results: Nine patients of the ITT set receiving lipegfilgrastim as primary prophylaxis (n = 222) had febrile neutropenia of grade 3–4 (5 patients) or infection of grade 3–4 (4 patients); 1/26 of those receiving secondary prophylaxis had an event. Dose reductions were performed in 9.5% of the patients. Postponement of cancer CT cycles for >3 days occurred in Conclusions: Application of lipegfilgrastim was effective as primary and secondary prophylaxis in the prevention of CT-induced neutropenia in breast cancer.

Thrombotic microangiopathy (TMA) is a rare but severe complication of tumors and their chemotherapeutic treatment. We report on two patients with chemotherapy-induced TMA who were successfully treated with a short course of the terminal complement inhibitor eculizumab. Both patients quickly achieved remission of microangiopathic hemolytic anemia and recovery of renal function. After withdrawal of eculizumab, remission was stable over an observation period of 47 months and 15 months, respectively. Our data show that eculizumab is effective in treating chemotherapy-induced TMA. Discontinuation of eculizumab is feasible once the complement-activating condition is controlled and the trigger is eliminated. Additional studies need to determine the optimal duration of complement-directed therapies and validate effective monitoring strategies after discontinuation of such therapy.

N-acetylcysteine (NAC) may be useful in the management of chemotherapy-induced liver injury. The present study evaluates the possible therapeutic effects of NAC on chemotherapy-induced hepatotoxicity. A total of 102 patients’ files who were diagnosed with cancer between 2015 and 2019 were evaluated retrospectively. Two patient groups with and without NAC were selected. NAC was administered in a 3-μg/kg IV dose in a 24-h infusion to 70 patients when any alanine aminotransferase (ALT) or gamma-glutamyl transferase (GGT) values reached three times the normal levels. The other group consisted of 32 patients who were not treated with NAC. Alanine aminotransferase and GGT values were recorded at pretreatment, and on the 1st, 3rd, 5th, and 7th days in both the NAC and non-NAC groups from files. In the NAC group, ALT and GGT values on day 1, 3, 5, and 7 differed from each other, decreasing from day 1 to day 7. A statistically significant difference was noted between the values in the NAC group (p

Purpose: Chemotherapy-induced nausea (CIN) is a relevant problem for gynaecological cancer patients. The evaluation of CIN is a key aspect in its management, along with the identification of associated risk factors. The objective of the study was to compare different measurements of nausea and to investigate personal risk factors in CIN development. Method: Eighty-one women treated for gynaecological cancers took part. The presence of CIN was evaluated using the MASCC Antiemesis Tool (MAT) and a patient’s report to clinicians at the subsequent chemotherapy cycle. Personal risk factors were assessed using the State-Trait Anxiety Inventory and a self-report questionnaire. Results: The study shows that the agreement between patients’ assessment of CIN with MAT and what they referred to clinicians was only moderate for acute nausea (Cohen’s Kappa = 0.55; p < 0.001), while good for delayed nausea (Cohen’s Kappa = 0.68; p < 0.001). At multiple logistic regression analysis, younger age, anticipatory nausea, patient medium-high expectations of CIN, and parity emerged as risk factors for the development of acute nausea (p = 0.0087, 0.0080, 0.0122 and 0.0021, respectively). Patient medium-high expectations of CIN and being single resulted to be risk factors for delayed nausea (p = 0.0397 and 0.0024, respectively). Conclusions: Our findings confirm that personal factors contribute to individual differences in the development of CIN; moreover, we highlight the importance of CIN evaluation by clinicians, underlining the need to usereliable instruments.

Chemotherapy treatment of malignancy accounts for 1–2% of takotsubo syndrome (TS) triggers. Women comprise 60–70% of patients with chemotherapy-associated TS, a distinctly lower prevalence than the 90% female prevalence in TS overall. Fluorouracil is the most commonly reported TS-triggering chemotherapeutic agent, although this must be interpreted in the context of the frequency of worldwide use of this agent. The onset of TS relative to chemotherapy initiation is quite variable, ranging from the initial administration to subsequent chemotherapy cycles several weeks beyond initiation. Limited information suggests chemotherapy can be safely reinitiated once the patient has recovered from the initial TS event. Having a TS event in the setting of chemotherapy treatment for malignancy is associated with substantial mortality.

Background Currently, the risk factors associated with chemotherapy-induced thrombocytopenia (CIT) in patients with diffuse large B-cell lymphoma (DLBCL) are still undefined. Our study aimed to analyze the effects of risk factors on thrombocytopenia and to identify the threshold for infusion platelets of CIT patients who have received platelet transfusions. Methods We conducted a retrospective analysis of 523 patients with DLBCL from 2011 to 2013. The clinical and demographic parameters were extracted, and the risk factors associated with CIT were analyzed. The threshold for platelet transfusions in DLBCL patients with a central venous catheter (CVC) was evaluated. Results A total of 227 (43.4%) DLBCL patients had thrombocytopenia, and 63 (12.0%) had thrombocytopenia without concomitant cytopenia. We found that the choice of chemotherapy regimen was positively correlated with thrombocytopenia (P

IntroductionLipegfilgrastim is a long-acting glycopegylated granulocyte-colony stimulating factor (G-CSF) used to prevent chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN). The aim of the current study was to obtain data on the drug efficacy and safety in real-world clinical practice.Material and methodsThis is an exploratory analysis of Polish breast cancer patients participating in a pan-European study of lipegfilgrastim in primary and secondary prophylaxis for patients receiving cytotoxic chemotherapy (Lonquex ObsErvational Cohort Study, LEOS). Patients were followed since the start of neutropenia prophylaxis until 6 to 8 weeks after the last dose of the lipegfilgrastim . The efficacy measures were chemotherapy dose reductions, omissions, delays and the proportion of the planned cumulative dose actually delivered.ResultsA total of 45 mostly high risk of FN patients were included in the analysis. Overall, 31 of 212 chemotherapy cycles (14.6%) were delayed in 19 patients (42.2%). Cumulative dose of chemotherapy was reduced in 1.4% of the cycles in 4.4% of the patients. The mean percentage of cumulative dose planned actually administrated was 99.95% across all cycles. Only one patient had FN. There were 15 episodes of neutropenia in 3 patients (6.7%), A total of 69 adverse events were reported, which 65% were drug-related. The most common were musculoskeletal pain (17.8%) and myalgia (11.1%) Four adverse events were serious and two of them were related to lipegfilgrastim.ConclusionsLipegfilgrastim proved to be effective and well-tolerated for CIN prophylaxis in patients with breast cancer receiving myelosuppressive chemotherapy in a real-life setting.

Objectives This study aimed to evaluate the effectiveness of topical application of olive oil either to delay chemotherapy induced oral mucositis (OM) or to alleviate its severity in Acute Lymphoblastic Leukemia children. Materials and methods a randomized controlled clinical trial was conducted at Hematology-Oncology Department of Children's Hospital of Damascus University, Syria. 24 children suffering from acute lymphoblastic leukemia aged between 4 and 6 years old were randomly assigned into two groups, olive oil and sodium bicarbonate 5% (12 in each group). Preventive protocol started two days before the induction of chemotherapeutic drugs. Topical application was done by a sterilized spongeous stick in order to swab tongue, buccal mucosa, floor of the mouth, lips and hard palate, as those tissues of the mouth are susceptible to chemotherapy induced OM [1]. The study period was within induction and consolidation phases of chemotherapy. Oral mucosa was assessed weekly up to eight weeks by two external investigators using the World Health Organization grading scale. Results Data was analyzed using Mann-Whitney U test. Based on the observed results, (OM) grades were with less severity in olive oil group than in sodium bicarbonate group with statistically significant difference reported from the 2 nd week of study phase. In addition, Mann-Whitney U test demonstrated that patients in olive oil group started (OM) later than those in sodium bicarbonate group with statistically significant difference (p = 0.022). As a result, olive oil retarded the beginning of oral mucositis (OM) compared with sodium bicarbonate. Conclusions olive oil can be used topically on oral tissues to prevent chemotherapy induced (OM) in acute lymphoblastic leukemia children.

Background: The existing risk prediction models for chemotherapy-induced febrile neutropenia (FN) do not necessarily apply to real-life patients in different healthcare systems and the external validation of these models are often lacking. Our study evaluates whether a machine learning-based risk prediction model could outperform the previously introduced models, especially when validated against real-world patient data from another institution not used for model training. Methods: Using Turku University Hospital electronic medical records, we identified all patients who received chemotherapy for non-hematological cancer between the years 2010 and 2017 (N = 5879). An experimental surrogate endpoint was first-cycle neutropenic infection (NI), defined as grade IV neutropenia with serum C-reactive protein >10 mg/l. For predicting the risk of NI, a penalized regression model (Lasso) was developed. The model was externally validated in an independent dataset (N = 4594) from Tampere University Hospital. Results: Lasso model accurately predicted NI risk with good accuracy (AUROC 0.84). In the validation cohort, the Lasso model outperformed two previously introduced, widely approved models, with AUROC 0.75. The variables selected by Lasso included granulocyte colony-stimulating factor (G-CSF) use, cancer type, pre-treatment neutrophil and thrombocyte count, intravenous treatment regimen, and the planned dose intensity. The same model predicted also FN, with AUROC 0.77, supporting the validity of NI as an endpoint. Conclusions: Our study demonstrates that real-world NI risk prediction can be improved with machine learning and that every difference in patient or treatment characteristics can have a significant impact on model performance. Here we outline a novel, externally validated approach which may hold potential to facilitate more targeted use of G-CSFs in the future. publishedVersion

Chemotherapy is a potential cause of focal and diffuse hepatobiliary lesions. Many of these lesions may be demonstrated on imaging, especially computed tomography and MRI. Some of these lesions, especially those of steatosis and sinusoidal obstruction syndrome, are associated with a worse prognosis and risk of hepatic failure in the context of surgical management. Notably, some chemotherapy-induced hepatic alterations, such as sinusoidal obstruction syndrome, pseudocirrhosis and focal hepatopathies, may be mistakenly interpreted as signs of cancer progression, misguiding the therapeutic planning for patients receiving chemotherapy.

PurposeDysgeusia is an adverse event caused by chemotherapy. Although retrospective studies have shown zinc administration improves dysgeusia, there have been no prospective studies. The present study examined effects of zinc therapy on dysgeusia in patients with gastrointestinal cancer.MethodsThis multicenter, prospective, observational study enrolled patients with dysgeusia during chemotherapy treatment. Patients received treatment of no intervention (control), polaprezinc p.o., or zinc acetate hydrate p.o. and serum zinc levels were measured at 0 (baseline), 6, and 12 weeks. Dysgeusia was assessed using CTCAE v5.0 and Subjective Total Taste Acuity (STTA) criteria using questionnaires at baseline and 12 weeks.ResultsFrom February 2020 to June 2021, 180 patients were enrolled from 17 institutes. There were no differences in mean serum zinc levels in each group at baseline (67.3, 66.6, and 67.5 μg/dL in the no intervention, polaprezinc, and zinc acetate hydrate groups, respectively. P = 0.846) and the mean changes in serum zinc level in the three groups from baseline to after 12 weeks were −3.8, +14.3, and +46.6 μg/dl, respectively. The efficiency rates of dysgeusia were 33.3%, 36.8%, and 34.6% using CTCAE and 33.3%, 52.6%, 32.7% using STTA in the no intervention, polaprezinc, and zinc acetate hydrate groups, respectively. The polaprezinc group showed a significantly improved STTA score compared with the no intervention group (P = 0.045).ConclusionThere was no significant correlation between the degree of serum zinc elevation and improvement in dysgeusia, suggesting that polaprezinc, but not zinc acetate hydrate, is effective in improving chemotherapy-induced dysgeusia.Trial registration number UMIN000039653. Date of registration, March 2, 2020.

Case report Pellagra is a systemic disease caused by a deficiency of vitamin B3 .A 19-year-old male patient, who was diagnosed with Burkitt's lymphoma was admitted to the hematology clinic for the second cycle of R-CODOX-M chemotherapy treatment. The patient at risk of malnutrition developed dermatit,diare and demans during treatment. The cause of diarrhea in the neutropenic patient is mostly in the form of infective diarrhea. Diarrhea due to vitamin deficiency should be kept in patients with malnutrition .