Complications In Cancer Patients Research Articles

Osimertinib: Another medication related to osteonecrosis of the jaws? A case report and literature review

Introduction: Medication-related osteonecrosis of the jaw (MRONJ) is an oral complication in cancer patients being treated with either antiresorptives, mainly denosumab and bisphosphonates, or antiangiogenic drugs. Osimertinib is a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) for the treatment of patients with EGFR T790M advanced non-small-cell lung cancer (NSCLC). TKI-induced osteonecrosis of the jaw has been reported in recent years, but these cases almost occur in combination with bisphosphonates, and the data on MRONJ associated to osimertinib is scarce. Case report: We reported a case of MRONJ associated only with osimertinib. A 69-year-old female patient with NSCLC developed MRONJ after 4 years of treatment with osimertinib. Six months ago, she felt persistent pain and swelling in the right maxilla. After 3 months of pain, her dentist extracted one tooth in the right maxilla under local anesthesia. We examined her gingiva and found fistula and pus spillage. A digital volume tomography scan revealed sequestrum. The patient underwent surgical debridement of the necrotic bone under general anesthesia and administered intravenous antibiotics at the hospital. Histopathological analysis of the bone biopsy revealed a diagnosis of MRONJ. Conclusion: This report provides evidence that osimertinib monotherapy can cause MRNOJ, and has a contribution to explore the formation mechanism of MRONJ. For those patients who take osimertinib, routine oral examinations and monitoring should be performed before and during treatment, as well as prompt closure of wounds and antibiotic treatment to avoid infection after invasive oral surgery such as tooth extraction.

Nutritional risk screening in malignant tumors: a study of 375 cancer inpatients.

Malnutrition is a common complication in cancer patients. It often accelerates disease progression and affects treatment outcomes. Thus, in the early census of cancer patients, examination for possible nutritional risks and correcting potential causes of malnutrition are needed to improve patients' quality of life. Our study included 375 patients diagnosed with cancer in Henan province and analyzed the relationship between nutritional risk and indicators like age, serum albumin, serum prealbumin, serum hemoglobin, tumor stage, tumor type, and inflammatory factors. We found that age, hemoglobin, and presence of gastrointestinal tumors were independent risk factors for nutritional risk. We also found significant correlation between inflammatory factors and nutritional risk in cancer patients, so as to provide new prediction indexes for clinical management of nutritional risk and dynamic changes of nutritional status.

Comparison of the effects of two different doses of Filgrastim in febrile neutropenia management in childhood malignancy: A randomized clinical trial

Background: Febrile neutropenia (FN) is most often caused due to chemotherapy. Solid or certain lymphoproliferative malignancies can increase the duration of hospitalization and other complications in cancer patients. Filgrastim is used in childhood FN management. This study aimed to compare the effect of two different doses of Filgrastim on hematological and paraclinical factors in hospitalized febrile neutropenic patients with cancer. 
 Materials and methods: In this randomized clinical trial, 60 febrile neutropenic patients with cancer complying with the inclusion criteria were assigned to both groups A and B. Thirty patients in group A received Filgrastim 5μg/kg/day whereas 30 others in group B received Filgrastim 15μg/kg/day. Hematological factors, physical examination findings, antibiotic administration period, and type of malignancy were then recorded. Complete blood count with differential (CBC diff) was also tested. Lung infiltration was examined by chest X-ray (CXR), and the spleen and abdomen were monitored by ultrasound.
 Results: The mean age of patients was 6 ± 3 years old. The most prevalent malignancies included acute lymphoblastic leukemia (ALL) (35.0%), neuroblastoma (18.3%), osteosarcoma (11.7%), acute myeloid leukemia (AML) (8.3%), and Rhabdomyosarcoma (8.3%). The frequency distribution of malignancies significantly differed between the two groups (P= .01). Changes in hematological factors, including white blood cells (WBC), mature neutrophil cells, and absolute neutrophil count (ANC) in group A, appeared lower than those in the other group. However, none of the studied factors, including hematological factors, physical examination findings, and antibiotic administration period, were found to differ significantly between the two groups (P> 0.05).
 Conclusion: Much as a higher dose of Filgrastim seems to bear a better effect on ANC, no significant difference was identified between the two groups. Further studies should be designed with a larger population to address the issue.

Neutrophil Extracellular Traps and Pancreatic Cancer Development: A Vicious Cycle.

Simple SummaryCancer-associated thrombosis is a significant complication in cancer patients with various clinical consequences. Neutrophil extracellular traps (NETs), are associated with cancer development and hypercoagulability in various cancers, including pancreatic cancer. On the other hand, pancreatic cancer development is associated with increased NETs formation. This feedback mechanism suggests the existence of a vicious cycle between NETs and the tumor microenvironment in pancreatic cancer, that supports tumor development and may lead to cancer-associated thrombosis.Neutrophil extracellular traps (NETs) are a neutrophil-generated extracellular network of chromatin and chromatin-bound molecules with antimicrobial potency. Recent data suggest that NETs are associated with cancer progression and cancer-associated hypercoagulability. Pancreatic adenocarcinoma (PDAC) is a lethal type of cancer in which hypercoagulability and cancer-related thrombosis are among the main complications. In the current report, we summarize the available data on the interplay between NET formation and PDAC development. We conclude that NETs support a dual role during PDAC progression and metastasis. Their formation is on the one hand an important event that shapes the cancer microenvironment to support cancer cell proliferation, invasion and metastasis. On the other hand, NETs may lead to cancer-associated thrombosis. Both mechanisms seem to be dependent on distinct molecular mechanisms that link inflammation to cancer progression. Collectively, NET formation may contribute to the pathogenesis of PDAC, while during cancer development, the proinflammatory environment enables the induction of new NETs and thrombi, forming a vicious cycle. We suggest that targeting NET formation may be an effective mechanism to inhibit both PDAC development and the accompanying hypercoagulability.

Distinct Metabolism of Bone Marrow Adipocytes and their Role in Bone Metastasis.

Bone marrow adipocytes (BMAs) represent 10% of the total fat mass of the human body and serve as an energy reservoir for the skeletal niche. They function as an endocrine organ by actively secreting fatty acids, cytokines, and adipokines. The volume of BMAs increases along with age, osteoporosis and/or obesity. With the rapid development of multi-omic analysis and the advance in in vivo imaging technology, further distinct characteristics and functions of BMAs have been revealed. There is accumulating evidence that BMAs are metabolically, biologically and functionally unique from white, brown, beige and pink adipocytes. Bone metastatic disease is an uncurable complication in cancer patients, where primary cancer cells spread from their original site into the bone marrow. Recent publications have highlighted those BMAs could also serve as a rich lipid source of fatty acids that can be utilized by the cancer cells during bone metastasis, particularly for breast, prostate, lung, ovarian and pancreatic cancer as well as melanoma. In this review, we summarize the novel progressions in BMAs metabolism, especially with multi-omic analysis and in vivo imaging technology. We also update the metabolic role of BMAs in bone metastasis, and their potential new avenues for diagnosis and therapies against metastatic cancers.

Do Antiangiogenics Promote Clot Instability? Data from the TESEO Prospective Registry and Caravaggio Clinical Trial.

Background Venous thromboembolism (VTE) is a common complication in cancer patients. Much of its morbidity stems from the development of fatal pulmonary embolisms (PE). Little is known about the factors involved in clot stability, with angiogenesis possibly being implicated. Methods The database is from the TESEO prospective registry that recruits cancer patients with VTE from 41 Spanish hospitals. Independent validation was conducted in a cohort from the Caravaggio trial. The objective is to evaluate the association between exposure to antiangiogenic therapies and the PE/VTE proportion in oncological patients. Results In total, 1,536 subjects were evaluated; 58.4% ( n = 894) had a PE and 7% ( n = 108) received antiangiogenic therapy (bevacizumab in 75%). The PE/VTE proportion among antiangiogenic-treated individuals was 77/108 (71.3%) versus 817/1,428 (57.2%) among those receiving other alternative therapies ( p = 0.004). The effect of the antiangiogenics on the PE/VTE proportion held up across all subgroups except for active smokers or those with chronic obstructive pulmonary disease. Exposure to antiangiogenics was associated with increased PEs, odds ratio (OR) 2.27 (95% CI, 1.42–3.63). In the Caravaggio trial, PE was present in 67% of the individuals treated with antiangiogenics, 50% of those who received chemotherapy without antiangiogenic treatment, and 60% without active therapy ( p = 0.0016). Conclusion Antiangiogenics are associated with increased proportion of PE in oncological patients with VTE. If an effect on clot stability is confirmed, the concept of thrombotic risk in cancer patients should be reconsidered in qualitative terms.

Abstract 3138: The lung pro-thrombotic niche drives cancer-associated thromboembolism via exosomal ITGB2

Abstract Thromboembolism (TE) is a common complication in cancer patients and the second leading cause of cancer-related deaths. The incidence of TE varies in different cancer types, with the highest risk in lung cancer and pancreatic ductal adenocarcinoma (PDAC), and in advanced-stage and metastatic cancers. Despite the benefits associated with thromboprophylaxis for symptomatic TE, the prevention of TE still remains an unmet clinical need due to lack of biomarkers predictive of TE risk and the bleeding risk associated with the routine use of anti-coagulants. Exosomes are small circulating extracellular vesicles that mediate cell-to-cell communication. Cancer cells and the tumor microenvironment release large numbers of exosomes into the blood circulation and have displayed a therapeutic and predictive value in systemic diseases. Integrins expressed on the surface of exosomes drive their selective organotropism and prepare distant sites for metastatic seeding by establishing favorable pre-metastatic niches. Here we show that exosomes from metastasis-bearing lungs or pre-metastatic lungs of mice with melanoma, breast, lung and pancreatic cancer induce TE in mice and express high levels of integrin beta 2 (ITGB2). Instead, exosomes from tumor cell lines, primary tumors or other metastasis-bearing organs did not show any pro-thrombotic properties. Myeloid cells including monocytes/macrophages and neutrophils infiltrating pre- and post-metastatic lungs were the main source of ITGB2+ pro-thrombotic exosomes. Blockade of ITGB2 on lung-derived exosomes, or systemically in mice, prevented exosome-induced platelet aggregation and TE, and reduced metastasis. Examination of the mechanisms of ITGB2-induced TE showed that exosomal ITGB2 interact directly or through fibrin with different binding partners on platelets, and induce their activation and aggregation. Importantly, we found that exosomal ITGB2 levels are elevated in the plasma of PDAC patients prior to TE events in comparison to PDAC patients with no history of TE, and thus might serve as prognostic biomarker of TE. Together, our results provide the first evidence of the establishment of a pro-thrombotic lung niche in different cancer types. Moreover, we identify exosomal ITGB2 as a new target for the prevention and/or treatment of TE, as well as a potential “liquid biopsy” analyte for the early stratification of patients at high risk of TE. Citation Format: Serena Lucotti, Yusuke Ogitani, Candia M. Kenific, Linda Bojmar, Michele Cioffi, Pernille Lauritzen, Henrik Molina, Soren Heissel, Harry B. Lengel, Xiaohong Jing, Haiying Zhang, Irina Matei, Eileen M. O'Reilly, William R. Jarnagin, David R. Jones, James B. Bussel, David Kelsen, Jacqueline F. Bromberg, Diane M. Simeone, David Lyden. The lung pro-thrombotic niche drives cancer-associated thromboembolism via exosomal ITGB2 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3138.

Immunoglobulin (IgG4) Sclerosing Cholecystitis-Camouflage for Gall Bladder Cancer- Case report and Review of Literature

It has been widely demonstrated that in patients with chronic diseases or cancer, iron homeostasis may be dysregulated. Iron deficiency with or without anemia is a frequent complication in cancer patients and may be associated.

Roles of Toll-Like Receptors in Radiotherapy- and Chemotherapy-Induced Oral Mucositis: A Concise Review

Radiotherapy and/or chemotherapy-induced oral mucositis (RIOM/CIOM) is a common complication in cancer patients, leading to negative clinical manifestations, reduced quality of life, and impacting compliance with anticancer treatment. The composition and metabolic function of the oral microbiome, as well as the innate immune response of the oral mucosa are severely altered during chemotherapy or radiotherapy, promoting the expression of inflammatory mediators by direct and indirect mechanisms. Commensal oral bacteria-mediated innate immune signaling via Toll-like receptors (TLRs) ambiguously shapes radiotherapy- and/or chemotherapy-induced oral damage. To date, there has been no comprehensive overview of the role of TLRs in RIOM/CIOM. This review aims to provide a narrative of the involvement of TLRs, including TLR2, TLR4, TLR5, and TLR9, in RIOM/CIOM, mainly by mediating the interaction between the host and microorganisms. As such, we suggest that these TLR signaling pathways are a novel mechanism of RIOM/CIOM with considerable potential for use in therapeutic interventions. More studies are needed in the future to investigate the role of different TLRs in RIOM/CIOM to provide a reference for the precise control of RIOM/CIOM.

PREDICTORS OF OVERALL SURVIVAL IN PATIENTS WITH MALIGNANT PLEURAL EFFUSION

TYPE: Abstract TOPIC: Disorders of the Pleura PURPOSE: Malignant pleural effusion (MPE) is a common complication in cancer patients, typically associated with a poor prognosis. We aimed to identify predictors of overall survival (OS) in patients with MPE. METHODS: We retrospectively analyzed patients with MPE between January 2012 and December 2018 in our hospital center. Demographic and clinical data were reviewed. We used Kaplan-Meyer analysis to estimate OS. Univariate and multivariate Cox-proportional-hazards regression models were used to identify factors associated with OS. RESULTS: There were 365 patients with MPE (52.1% were male, mean age of 68.0±12.5 years), 32.3% with an ECOG-PS-score ≥2. Lung cancer was the most prevalent malignancy. Specific cancer treatment was given to 241 patients and pleurodesis was performed in 90 cases. During the follow-up period, 332 patients died. The median time from MPE diagnosis to death was 15.0 (4.0-56.0) weeks. In univariate analysis, male sex (p=0.001), ECOG-PS≥2 (p≤0.001), colorectal-cancer (p=0.018), gastric-cancer (p≤0.001), occult-cancer (p≤0.001) and pleurodesis recurrence (p=0.021) were associated with worse OS; in contrast, breast-cancer (p=0.008) and hematological-cancer (p=0.045), systemic treatment (p≤0.001) and pleurodesis (p=0.034) were significantly associated with better OS. According to the multivariate analysis, male sex (HR:1.32; p=0.021), ECOG-PS≥2 (HR:1.93; p≤0.001), lung-cancer (HR:1.54; p=0.018), colorectal-cancer (HR:3.01; p=0.006), gastric-cancer (HR:2.08; p=0.001), occult-cancer (HR:2.16; p=0.013) and systemic treatment (HR:0.32; p≤0.001) were independent predictors of OS. CONCLUSIONS: In our study, we confirmed that MPE is associated with poor prognosis. CLINICAL IMPLICATIONS: There was a worse prognosis in male patients, with a higher ECOG-PS-score and certain types of cancer (lung, colorectal, gastric and occult), as well as in non-candidates for systemic treatment. DISCLOSURE: Nothing to declare. KEYWORD: Malignant pleural effusion, survival, predictors

Increased risk of venous thrombosis in breast cancer patients receiving chemotherapy treatment after COVID-19.

e24106 Background: Immune suppression and coagulopathy development in cancer patients receiving chemotherapy determines a high incidence of complications, including venous thrombosis, and mortality from COVID-19 infection. There are still no explicit data on managing cancer patients when anticancer treatment is resumed after coronavirus disease. According to clinical guidelines for the prevention of venous thromboembolic complications in cancer patients receiving chemotherapy, patients with breast cancer are classified as having a low risk of these complications and do not require prophylactic anticoagulation. The purpose of this study was to assess the parameters of the blood coagulation system and the frequency of venous thrombosis in breast cancer patients with chemotherapy resumption after coronavirus disease. Methods: The study included 30 patients receiving anticancer medical therapy for breast cancer after COVID-19. Anticancer treatment was resumed no earlier than 4 weeks after clinical recovery, absence of SARS-CoV-2 RNAs in nasopharyngeal swabs, infiltrative lung damage according to a chest CT scan, exclusion of venous thrombosis by a lower extremity venous ultrasound. Control group included 20 breast cancer patients without a history of COVID-19. Stage I tumors were registered in 26.6% in the main group vs 15% controls; II - 40% vs 60%; III - 20% vs 15%. Some patients were diagnosed with distant metastases (stage IV- 13.3% vs 10%). Results: Initially, before chemotherapy resumption in the main group, half of the patients had elevated levels of fibrinogen and D-dimer compared with the control group (66.7% vs. 35%, p > 0.05). After a cycle of chemotherapy, a significant difference in the coagulation system parameters was noted (73.3% vs 30%). A lower extremity venous ultrasound after the end of the therapy cycle in the main group showed venous thrombosis in 3 patients (catheter-related n = 2, distal vein thrombosis of the lower extremities n = 1), while no venous thrombotic complications were detected in the control group (10% vs. 0%). Conclusions: Breast cancer patients after coronavirus disease 2019 have hemostasis abnormalities and higher risk of venous thrombosis, and the resumption of anticancer treatment increases the incidence of thrombotic complications. COVID-19 should be considered an additional risk factor of venous thrombosis in cancer patients and requires reconsideration of indications for prophylactic anticoagulation when resuming anticancer treatment for patients with breast cancer.

Venous thromboembolic events in glioblastoma patients: An epidemiological study.

Background and purposeVenous thromboembolic events (VTEs) are a major complication in cancer patients, and therefore, also in brain cancer patients, anticoagulants are considered appropriate in the treatment of VTEs.MethodsFrequency, risk factors, and treatment of VTEs, as well as associated complications, were assessed in a population‐based cohort of glioblastoma patients in the Canton of Zurich, Switzerland. Correlations between clinical data and survival were retrospectively analyzed using the log‐rank test and Cox regression models.ResultsFour hundred fourteen glioblastoma patients with isocitrate dehydrogenase wild‐type status were identified. VTEs were documented in 65 patients (15.7%). Median time from tumor diagnosis to the occurrence of a VTE was 1.8 months, and 27 patients were diagnosed with VTEs postoperatively (within 35 days; 42.2%). History of a prior VTE was more common in patients who developed VTEs than in those who did not (p = 0.004). Bevacizumab treatment at any time during the disease course was not associated with occurrence of VTEs (p = 0.593). Most patients with VTEs (n = 61, 93.8%) were treated with therapeutic anticoagulation. Complications occurred in 14 patients (23.0%), mainly intracranial hemorrhages (n = 7, 11.5%). Overall survival did not differ between patients diagnosed with VTEs and those who had no VTE (p = 0.139). Tumor progression was the major cause of death (n = 283, 90.7%), and only three patients (1.0%) died in association with acute VTEs.ConclusionsVenous thromboembolic events occurred early in the disease course, suggesting that the implementation of primary venous thromboembolism prophylaxis during first‐line chemoradiotherapy could be explored in a randomized setting.

Atrial fibrillation in cancer patients who develop stroke

BackgroundAcute ischemic stroke (Stroke) and transient ischemic attacks (TIA) are known complications in cancer patients and those with atrial fibrillation (AF). The role AF plays in Stroke/TIA in the setting of cancer is unclear. The purpose of this study was to assess the relationship between AF and Stroke/TIA in cancer patients.MethodsWe conducted a case-control study comparing all patients who developed Stroke/TIA from 2014 to 2019 following a cancer diagnosis at King Hussein Cancer Center (KHCC), matched to Stroke/TIA-free controls based on age, gender, and cancer site.ResultsTwo hundred seventy-two patients were included (136 per group). The mean age was 63.95 ± 13.06 and 57% were females. The Stroke/TIA group had more AF at the time of event (14% vs. 4%, OR: 4.25, 95%-CI: 1.39 - 17.36) and had a larger proportion of death on study conclusion (OR: 9.4, 95%-CI: 3.74 - 23.64). On conditional logistic regression, patients in the Stroke/TIA group had higher odds of: AF (OR: 7.93, 95%-CI: 1.6 – 39.18), ischemic stroke before cancer diagnosis (OR: 9.18, 95%-CI: 2.66 – 31.74), being on active cancer treatment (OR: 3.11, 95%-CI: 1.46 – 6.62), dyslipidemia (OR: 3.78, 95%-CI: 1.32 – 10.82), and renal disease (OR: 4.25, 95%-CI: 1.55 – 11.63). On another conditional logistic regression model built to assess the role of the CHA2DS2-VASc score, a score of >=2 in males and >=3 in females significantly increased the risk of developing Stroke/TIA in cancer patients (OR: 2.45, 95%-CI: 1.08 - 5.58).ConclusionAF, previous ischemic stroke, active cancer treatment, dyslipidemia, and renal disease are independent risk factors for Stroke/TIA and a higher CHA2DS2-VASc score significantly increases the risk in cancer patients regardless of AF.

A prediction model for central venous catheter-related thrombosis in patients with newly-diagnosed acute myeloid leukemia: A derivation cohort analysis

BackgroundCatheter-related thrombosis (CRT) is a common complication in cancer patients, that may lead to chemotherapy deferral, elevated risk for systemic infections and pulmonary embolism. This study aimed to assess CRT incidence and risk factors in newly-diagnosed acute myeloid leukemia (AML) patients and create predictive models potentially allowing to decrease CRT occurrence in this population. MethodsThis retrospective single-center analysis included all AML patients treated at the Rambam Health Care Campus between 2006 and 2019. Patient clinical and laboratory data were collected to evaluate thrombosis occurrence and time from AML diagnosis to CRT development. Multivariate classification models were created using logistic regression (LR) and competing risk analyzes. ResultsThe final analysis included 632 newly-diagnosed AML patients (mean age 54 ± 15 years). CRT incidence was 10.1% [confidence interval (CI) 7.7–12.9%], median time from AML diagnosis to CRT was 12.5 days [interquartile range 6–30]. In an LR multivariate model, prior history of venous thromboembolism [adjusted odds ratio (AOR) 12.046, p < 0.0001], acute promyelocytic leukemia (APL) (AOR 2.824, p = 0.015), a high body mass index and initial platelet counts <100 × 10E9/L (AOR 1.059 and 0.546; p = 0.011 and 0.040, respectively) were significantly associated with high CRT risk. Analysis of 587 non-APL patients demonstrated comparable results, with CRT incidence of 9.3% (CI 7.0%-12.1%) and emergence of chronic obstructive pulmonary disease (COPD) as a novel significant co-factor (AOR 34.491, p = 0.004). In both models, the area under curve (AUC) was ≥70%. ConclusionsSignificant CRT risk factors defined using the created model could be used for identification of high-risk newly-diagnosed AML patients requiring CRT prophylaxis.

Clonal hematopoiesis and cardiovascular disease in cancer patients and survivors

Cancer genomes have long been known to carry a high number of somatic mutations distributed across many genes. However, recent sequencing studies have unveiled that non-cancerous cells also carry a considerable number of somatic mutations, which are acquired continuously through the lifespan. Accordingly, the pathophysiological relevance of somatic mutagenesis beyond cancer has become a topic of intensive research. Human genetic studies and experiments in mice have shown that some somatic mutations in the hematopoietic system provide a competitive advantage to the mutant cell and allow its clonal expansion. This phenomenon, termed clonal hematopoiesis, is typically driven by mutations in known oncogenes and tumor suppressor genes, and it is associated with a higher risk of hematological malignancies. Unexpectedly, accumulating genetic and experimental evidence strongly suggest that clonal hematopoiesis, at least when driven by certain mutations, also contributes causally to the development of cardiovascular disease and, therefore, represents a new cardiovascular risk factor. While clonal hematopoiesis is relatively common in healthy individuals, especially among the elderly, it is particularly frequent in cancer patients and survivors. Hence, it has emerged as a candidate contributor to the increased risk of cardiovascular complications in cancer patients. This review summarizes our current understanding of the connection between clonal hematopoiesis and cardiovascular disease, with a special focus on the available evidence linking clonal hematopoiesis to cardiovascular disorders that are frequent in cancer patients and survivors.

Cardiovascular toxic effects of antitumor agents: Pathogenetic mechanisms

Cancer treatment is associated with various side effects of antitumor agents, which increase the morbidity and mortality of these patients. Cardiovascular complications are considered to be one of the most important side effect of the anticancer drugs. The antitumor drugs that express cardiovascular effects include anthracyclines, tyrosine kinase inhibitors, taxanes, fluoropyrimidines, alkylating agents, vascular endothelial growth factor inhibitors, immune checkpoint inhibitors, proteasome inhibitors and human epidermal growth receptor type 2 antibodies. The spectrum of cardiovascular effects of anticancer drugs is broad and include, among others, heart failure, arrhythmias such as atrial fibrillation and ventricular tachyarrhythmias, hypertension (systemic or pulmonary), cardiomyopathy, myocarditis, valve disease, pericardial disease, vascular events (arterial thrombosis, venous thromboembolism) and myocardial ischemia (acute coronary syndrome, angina). The molecular mechanisms by which anti-cancer therapies lead to cardiotoxicity are diverse and vary according to the specific type of agent used. They include oxidative stress, topoisomerase 2-β inhibition in cardiomyocytes, inflammation, endothelial dysfunction, apoptosis, disruption of Ca2+ homeostasis, mitochondrial dysfunction, DNA damage, increase in various circulating microRNAs levels, alterations in the function of voltage-gated potassium channels. The management of cardiovascular complications in cancer patients is a new challenge for oncologists and cardiologists. Thus the cardio-oncology field has developed the last decade in order to precisely predict and efficiently treat the cancer treatment-related cardiovascular diseases.

Old is new again: Emergence of thromboembolic complications in cancer patients on immunotherapy

Cancer immunotherapy has emerged as one of the most important new treatments for cancer in many years, moving rapidly to front-line therapy for several cancers. Cancer immunotherapy is based on treatment with immune checkpoint inhibitors (ICI), which are monoclonal antibodies directed toward immunoregulatory proteins including PD-1, PD-L1 and CTLA-4. ICI inhibit interactions between these proteins and their ligands, disabling physiologic immune regulatory networks and enhancing anti-tumor immunity. However, since the immune response cannot be directed specifically to the tumor, ICI are associated with immune-related adverse events (irAEs) resulting from immune-mediated attack of normal tissues. We and others have reported a high incidence of thrombosis in patients treated with ICI, which may approach 20%. Given the rapidly increasing use of ICIs, it is clear that ICI-Associated Thrombosis (IAT) is a major emerging clinical problem. However, there is a remarkable knowledge gap concerning mechanisms of IAT. IAT may be a composite irAE resulting from activation of blood and vascular cells, leading to thromboinflammation. Cancer itself is an inflammatory disorder, and inducing further inflammation through ICI administration may stimulate procoagulant activity by multiple cell types. Moreover, some blood and vascular cells express ICI target proteins. Here, we review the results of several studies describing the clinical manifestations of IAT, as well as our recent studies demonstrating that elevated levels of myeloid derived suppressor cells and inflammatory cytokines may serve as biomarkers of IAT. It is hoped that the concepts reviewed here may stimulate further research into this important clinical problem.

T014 The significance of the study of detoxification efficiency of serum albumin for early diagnosis and monitoring of purulent-septic complications in cancer patients

T014 The significance of the study of detoxification efficiency of serum albumin for early diagnosis and monitoring of purulent-septic complications in cancer patients

Oral Complications in Cancer Patients-Medication-Related Osteonecrosis of the Jaw (MRONJ).

Medication-Related Osteonecrosis of the Jaw (MRONJ) was first reported in 2003. Despite the progress in the understanding of this oral complication in cancer patients for the past 18 years, there is still discussion about the best way to define MRONJ, prevent the complication, how to diagnose, and the options of treatment available. The initial reports associated MRONJ to bisphosphonates and denosumab, medications that work as bone-modifying agents. Later, other agents such as the antiangiogenics, have also been reported to cause the oral complication, either alone or in combination with antiresorptives. Initially, these medications were prescribed to patients with osteoporosis and cancers patients with bone metastasis. Today, because of the effect of the medications in the bone remodeling system, patients with several other diseases such as giant cell tumors, rheumatoid arthritis, Paget's disease of bone, fibrous dysplasia, osteogenesis imperfecta, are managed with these medications, significantly increasing the population of individuals at risk for developing MRONJ. This mini review focused on the cancer patient. It updates the dental clinician on the recent scientific literature about MRONJ and provides information on how to diagnose and manage patients being treated with these medications, suggests protocols to prevent the development of MRONJ, and present ways to manage those patients who develop the oral complication.

An Overview of Clinical Oncology and Impact on Oral Health.

As the incidence of cancer continues to increase, so too will the use of various forms of cancer therapeutics and their associated oral and dental complications. Although many of the acute and chronic oral toxicities of cancer therapy are largely unavoidable, appropriate and timely management of these complications has the potential to alleviate morbidity and improve outcomes. Undoubtedly, the substantial short- and long-term impacts of cancer therapy on the health of the oral cavity requires increased awareness, prevention, and treatment by multidisciplinary healthcare teams consisting of medical oncologists, dentists, and other oral healthcare specialists. This mini review provides a brief purview of the current state of clinical oncology and its impact on oral health. The topics introduced here will be further investigated throughout the remainder of the “Oral Complications in Cancer Patients” mini-review series.