Complications In Cancer Patients Research Articles

Temporal trends in inpatient outcomes and resource utilization in patients with tumor lysis syndrome (TLS) with solid and hematologic cancers: A nationwide analysis.

e19102 Background: Tumor lysis syndrome (TLS) is a well-recognized complication in cancer patients with high tumor burden receiving chemotherapy and is associated with increased morbidity and mortality. Our study specifically looks at longitudinal trends in outcomes and healthcare utilization in TLS patients over time. Methods: Adult patients with TLS admitted between 2012-2017 were identified from the Nationwide Inpatient Sample database. Statistical tests for trends of outcomes (including mortality and Acute Kidney Injury (AKI)) and resource utilization across six years were performed. Multivariable logistic regression was used to evaluate risk factors for mortality in TLS. Results: A total of 57,760 patients met inclusion criteria, with 15.2% having Solid Tumors (ST) and rest hematological cancers (HC). Patients with ST were predominantly older (mean age 60.7 vs 56.4 years, p < 0.0001) and female (44.6% vs 35.2%, p < 0.0001). ST patients had higher mortality (32.3% vs 19.1, p < 0.0001) and AKI (68.6% vs 59.3%, p < 0.0001); but shorter hospitals stay (10.5 vs 15.8 days, p < 0.0001) and lower hospital charges ($34k vs $59k, p < 0.0001). Multivariable analysis showed increased inpatient mortality with ST compared to HC (OR 1.54, 95% CI 1.35-1.76, p < 0.001). Although mortality in ST non-significantly decreased from 36.2% to 28.9% over time, it remained constant in HC. Rate of AKI increased significantly in both cohorts. There were no significant temporal changes in hospital charges in either group, although those with HC were noted to have a decrease in length of stay, from 16.8 to 15.6 days (p = 0.02) over time. Trends of outcomes and resource utilization in TLS. Conclusions: TLS in ST has worse prognosis than HC, although mortality has improved over years. However, inpatient mortality remains largely unchanged in HC. Despite therapeutic advances, [Table: see text]

PCN223 INCREMENTAL HEALTHCARE UTILIZATION AMONG CANCER PATIENTS WITH CARDIOVASCULAR DISEASES (CVD) AS COMPARED TO THOSE WITHOUT CVD IN THE UNITED STATES

The burden of cardiovascular diseases (CVD) and cardiac complications in cancer patients has increased in the recent past. Identifying the drivers of incremental utilization in cancer patients with CVD would help in containing costs and manage the condition better. The objective of our study was to estimate the incremental healthcare utilization of cancer patients with CVD compared to those without CVD.

Ancient Chinese Medicine Herbal Formula Huanglian Jiedu Decoction as a Neoadjuvant Treatment of Chemotherapy by Improving Diarrhea and Tumor Response.

BackgroundDiarrhea is a major gastrointestinal complication in cancer patients receiving chemotherapy. Prognosis and treatment of chemotherapy-induced diarrhea (CID) remain unsatisfactory. This study aims to explore the potential of an ancient Chinese Medicine herbal formula Huanglian Jiedu Decoction (HLJDD) as an adjuvant treatment on CID.MethodHLJDD extract was prepared by GMP manufacturing standard with quality and stability being checked. 5-fluorouracil (5-Fu) and irinotecan (CPT-11)-induced diarrhea model in mice was established and pre-, co- and post-treatment of HLJDD was implemented. Mechanism of action was explored by detecting related protein expression. In addition, the effect of HLJDD on diarrhea and tumor response induced by clinical regimens FOLFOX and FOLFIRI was measured in murine orthotopic colorectal cancer model.ResultsHLJDD exhibited consistency in quality and stability after 24-month storage. Pre-treatment of HLJDD, but not co-treatment or post-treatment, could significantly improve the diarrhea score, body weight loss and intestinal damage in 5-Fu- and CPT-11-treated mice. Pre-treatment of HLJDD reduced cell apoptosis in the intestine of chemotherapy-treated mice, and promoted renewal of intestinal cell wall. CD44 was predicted as the potential target of HLJDD-containing compounds in CID. HLJDD pre-treatment induced presentation of CD44-postive cells in the intestine of chemotherapy-treated mice, and initiated expression of stemness-associated genes. Transcriptional products of the downstream Wnt signaling of CD44 were elevated. Furthermore, pre-treatment of HLJDD could significantly improve the tumor response of clinical chemotherapy regimens FOLFOX and FOLFIRI in orthotopic colorectal cancer, and reduce diarrhea and intestinal damage. Conclusion: Our study suggests the potential of HLJDD as a neoadjuvant treatment of chemotherapy by reducing diarrhea and improving tumor response.

SIRT1 Mediates Effects of FGF21 to Ameliorate Cisplatin-Induced Acute Kidney Injury.

Acute kidney injury (AKI) is a common complication in cancer patients. Kidney function is closely related to patients’ quality of life and tumor prognosis. Cisplatin is a highly effective anti-tumor drug. However, the use of cisplatin is limited by its nephrotoxicity. It has been reported that FGF21 has a renal-protective function, but the mechanisms by which it does so remain unclear. In this study, we show that the expression of FGF21 is significantly upregulated in both in vitro and in vivo cisplatin-induced AKI models. Administration of recombinant FGF21 to cisplatin-induced AKI mice resulted in significantly decreased blood urea nitrogen (BUN) and serum creatinine levels, as well as significantly reduced protein levels of kidney injury molecule-1 (TIM-1), C-caspase 3, and Bax. H&E-stained kidney sections from cisplatin-induced AKI mice treated with recombinant FGF21 showed a relatively normal renal tissue structure, a reduced number of necrotic sites and vacuolar changes, and decreased casts, suggesting alleviated renal tubular injury. Experiments with an AKI cell model (cisplatin-treated HK-2 cells) yielded similar results as the mouse model; recombinant FGF21 significantly downregulated protein expression levels of TIM-1, C-caspase 3, and Bax. Furthermore, administration of recombinant FGF21 to cisplatin-treated AKI models significantly increased SIRT1 expression, and the beneficial effects of FGF21 on kidney injury were reversed by SIRT1 knockdown. Collectively, our results suggest that SIRT1 mediates the protective effect of FGF21 on cisplatin-induced kidney injury.

Cancer cachexia and its pathophysiology: links with sarcopenia, anorexia and asthenia.

Cancer cachexia is a multifactorial syndrome characterized by a progressive loss of skeletal muscle mass, along with adipose tissue wasting, systemic inflammation and other metabolic abnormalities leading to functional impairment. Cancer cachexia has long been recognized as a direct cause of complications in cancer patients, reducing quality of life and worsening disease outcomes. Some related conditions, like sarcopenia (age‐related muscle wasting), anorexia (appetite loss) and asthenia (reduced muscular strength and fatigue), share some key features with cancer cachexia, such as weakness and systemic inflammation. Understanding the interplay and the differences between these conditions is critical to advance basic and translational research in this field, improving the accuracy of diagnosis and contributing to finally achieve effective therapies for affected patients.

ATRIAL FIBRILLATION IN ACTIVE CANCER PATIENTS WHO DEVELOP STROKES

Background: Stroke and transient ischemic attacks (TIA) are known complications in cancer patients and in patients with atrial fibrillation (AF). It is unclear how commonly AF is diagnosed in the setting of active cancer complicated by stroke. The purpose of this study was to assess the relation

A multicenter retrospective investigation on the efficacy of perioperative oral management in cancer patients.

Patients develop a number of oral complications during cancer treatments. Oral bacteria are associated with the onset of dental focal infections and the progression of oral mucositis. Dental focal infections are frequently associated with the systemic onset of bacteremia, sepsis, and pneumonia. The degeneration of oral function with these complications may become an obstacle to cancer treatments. Although comprehensive oral management, including oral care, the removal of dental focal infections, and improvements in oral function with dentures, is conducted for cancer patients in Japan, few studies have assessed its efficacy.The aim of the present study was to investigate the incidence of dental/oral complications in cancer patients with perioperative oral managements (POMs) based on a large number of case series with a multicenter retrospective analysis.The medical records of cancer patients with POMs were retrospectively reviewed and the incidence of oral complications and efficacy of oral management were investigated.A total of 2744 cancer patients with POMs (1684 males and 1080 females, mean age 65.9 ± 13.0 years) were included and investigated in the present study. Among these patients, 2097 (76.4%) started POM before the initiation of cancer treatments, with 2130 (77.6%) receiving oral care only and 391 (14.2%) being subjected to invasive treatments, such as tooth extraction. The incidence of dental focal infections during the period of cancer treatments was 8.2%. The most frequent infection was acute periodontitis, including alveolar abscesses (112 patients, 4.1%). The incidence of grade 2 and 3 oral mucositis was 2.8%. Prolonged fever was observed in 113 patients (4.1%), with 7 having dental focal infections (6.2%). These incidence rates were lower than those reported previously.Based on analyses of a large number of patients, the present results support the efficacy of oral management in cancer patients. However, further studies are needed to establish adequate oral management guidelines for cancer patients.

Management of Anemia in Cancer Patients

Anemia is a frequent complication in cancer patients. Cancer-related anemia adversely affects quality of life and is associated with reduced overall survival. Reasons for anemia in cancer patients are decreased production of RBCs resulting from nutritional deficiencies; insufficient production of RBCs because of the presence of chronic disease; Cancer promotes inflammatory cytokine production, which suppresses erythropoiesis and erythropoietin (EPO) production; bone marrow infiltration by the tumor or bone marrow suppression resulting from anticancer treatment such as surgery, chemotherapy, or radiotherapy; and increased loss of RBCs caused by blood loss from the tumor, surgery, or hemolysis. Correction of anemia can be achieved by different methods.Treatment is aimed at increasing the oxygen-carrying capacity of the blood, reducing fatigue, and improving the patient's overall quality of life. Erythropoiesisstimulating agents, iron supplementation, and red blood cell transfusions have all been recommended in different settings.
 Anwer Khan Modern Medical College Journal Vol. 11, No. 1: Jan 2020, P 66-72

Palliative sedation for delirium management at the end of life

Delirium is a frequent neurocognitive complication in cancer patients, particularly in advanced stage and terminal disease. It is associated with increased morbidity and mortality and is a critical source of stress for patients and caregivers. For healthcare staff, delirium poses significant challenges in diagnosis and treatment as well as assessment of other symptoms due to its fluctuating nature, communication impediments, and possible agitation in hyperactive subtypes. Pathophysiological mechanisms underlying delirium are complex, but the approach to adequate symptom management consists of nonpharmacological strategies as well as the use of antipsychotic agents. However, when nonreversible and refractory delirium occurs, palliative sedation is an invaluable treatment option and may be offered after careful consideration. This short review attempts to cover important aspects of clinical features of delirium, diagnostic and treatment strategies as well as the role of palliative sedation in refractory situations in delirious cancer patients at the end of life.

Management of cancer-related thrombosis in the era of direct oral anticoagulants: A comprehensive review of the 2019 ITAC-CME clinical practice guidelines. On behalf of the Groupe Francophone Thrombose et Cancer (GFTC).

Venous thromboembolism (VTE) is a common disease complication in cancer patients and the second cause of death after cancer progression. VTE management and prophylaxis are critical in cancer patients, but effective therapy can be challenging because these patients are at higher risk of VTE recurrence and bleeding under anticoagulant treatment. Numerous published studies report inconsistent implementation of existing evidence-based clinical practice guidelines (CPG), including underutilization of thromboprophylaxis, and wide variability in clinical practice patterns across different countries and various practitioners. This review aims to summarize the 2019 ITAC-CME evidence-based CPGs for treatment and prophylaxis of cancer-related VTE, which include recommendations on the use of direct oral anticoagulants specifically in cancer patients. The guidelines underscore the gravity of developing VTE in cancer and recommend the best approaches for treating and preventing cancer-associated VTE, while minimizing unnecessary or over-treatment. Greater adherence to the 2019 ITAC guidelines could substantially decrease the burden of VTE and improve survival of cancer patients.

Novel Silver-Platinum Nanoparticles for Anticancer and Antimicrobial Applications.

BackgroundCancer is a disease with an enormous worldwide impact. One of the fatal complications in cancer patients are bacterial opportunistic infections. The use of chemotherapeutic drugs made cancer remission more frequent and prolonged patient survival, but, increased the risk of infections.PurposeAddress the current problem with growing pandemic cancer and considering high risks of complications with bacterial infections, the present study synthesized novel dendritic assembly of silver (Ag)-platinum (Pt) nanoparticles.MethodsNanoparticles were characterized by TEM analysis, and the composition was confirmed by EDX. Bacterial studies were performed for Gram-positive Staphylococcus aureus, Gram-negative Pseudomonas aeruginosa and Gram-negative multi-drug resistant Escherichia coli. Cell experiments were performed with two different cancer cell lines, glioblastoma and melanoma to determine anticancer activity. Finally, cytotoxicity with fibroblast was tested.ResultsThe TEM analysis of silver-platinum (AgPt) nanoparticles showed dendrimer shape nanoparticles with a mean size of 42 ± 11nm. Elemental composition was analyzed by EDX, confirming the presence of both Ag and Pt metals. The synthesized nanoparticles significantly inhibited the growth of medically important pathogenic, Gram-positive Staphylococcus aureus, Gram-negative Pseudomonas aeruginosa and Gram-negative multi-drug resistant Escherichia coli. Bactericidal effect of AgPt nanoparticles had greater effectiveness than silver nanoparticles. MTS assay revealed a selective and dose-dependent anticancer activity of AgPt nanoparticles over cancer cell lines glioblastoma and melanoma in the 10–250 µg/mL concentration range. Cytotoxicity experiments with fibroblast cells showed no side effects of nanoparticles against healthy cells at a range of concentrations from 10–50 µg/mL.ConclusionThe newly synthesized AgPt nanoparticles have a promising future as a potent anticancer agent with antibacterial properties.

Direct oral anticoagulants for thromboprophylaxis in ambulatory patients with cancer

ABSTRACT Background: Venous thromboembolism (VTE) is a common complication in cancer patients. We aim to evaluate the effect and safety of direct oral anticoagulants (DOACs) as primary prophylaxis in ambulatory cancer patients. Methods: We conducted a literature search in PubMed, EMBASE and ClinicalTrials for studies that evaluated DOACs for thromboprophylaxis in cancer patients. RevMan 5.3 software was used for this meta-analysis. Results: Three randomized controlled trials (RCTs) with a total of 1465 patients were pooled in the meta-analysis. DOACs significantly reduced the symptomatic VTE incidence during intervention period (RR 0.23, CI 0.11-0.47, P<0.0001, I2 =9%). Significantly lower total VTE incidence (RR 0.53, CI 0.36-0.78, P = 0.001, I2 =30%) and PE incidence (RR 0.50, CI 0.28-0.89, P = 0.02, I2 =5%) were found during the observation period, and a trend for less symptomatic DVT events was found in the DOACs group (RR 0.62, CI 0.37-1.04, P = 0.07, I2 =5%). No differences for all-cause mortality were found between groups (RR 0.92, CI 0.74-1.15, P = 0.47, I2 =14%). DOACs did not significantly increase major bleeding risks (RR 1.66, CI 0.72-3.83, P = 0.24, I2 =0%) during the intervention period or clinically relevant non-major bleeding events (RR 1.50, CI 0.90-2.49, P = 0.12, I2 =0%) and total bleeding events during the observation period (RR 1.50, CI 0.98-2.29, P = 0.06, I2 =0%). Conclusion: DOACs are effective for thromboprophylaxis in ambulatory cancer patients, but there is a potential risk of bleeding. DOACs may be recommended in selected patients at high risk of VTE. More high-quality studies are needed to further validate our results. Abbreviations: CAT: cancer-associated thrombosis; CI: confidence interval; DOAC: direct oral anticoagulant; DVT: deep vein thrombosis; LMWH: low molecular weight heparin; NNH: number needed to harm; NNT: number needed to treat; PE: pulmonary embolism; RCT: randomized controlled trials; RR: risk ratio; RD: rate difference; VTE: venous thromboembolism.

A Survey of the Cardiology Care Delivered to Cancer Patients in Nigeria

BACKGROUND: The incidence of cardiovascular disease is on the rise and this is no less so amongst the population of individuals who are affected by cancer as improvement over the years in cancer treatment options have brought about improved outcomes in terms of overall patient survival and outcomes but has additionally also illuminated the side effects of these cancer treatment as patients live longer to manifest them thereby increasing morbidity and mortality. In Nigeria, there is paucity of data on cardio-oncology and this study will be the first documented study assessing the level of knowledge and the activity of cardiology care provided to oncology patients who develop cardiovascular disease in Nigeria and will therefore serve as a template towards the development of cardio-oncology services in Nigeria. METHODS: The survey was questionnaire-based involving cardiologist in Nigeria. They first part assessed the demographic characteristics of participants. The second part of the questionnaire assessed participants’ self-admitted expertise in the management of cardiovascular conditions complicating cancer treatment. RESULTS: There were more male (57.14%) than female (42.86%) respondents. More than two-thirds of respondents (71.4%, n=55) were aged 30-44 year. Cumulatively, the South-south and South-western regions accounted for over two-thirds of responses (72.43%, n=55). Over three-thirds of respondents (83.12%, n=) worked at teaching hospitals. Majority (89.5%, n=68) of ambulatory cancer patients in need of cardiology care received this service in a general cardiology clinic with only 10.5% (n=8) receiving care at a cardio-oncology centre. Majority of respondents (67.1%, n=51) dId not receive referrals from general practitioners or other specialists to evaluate cardiac problems in patients who had received cancer treatment. 80.5% of participants (n=62) said that they either did not know about the ESC position paper or knew about it but did not apply its suggestions to their practice. CONCLUSION: Most cancer patients requiring cardiovascular care are seen in the general cardiology clinic of Government owned hospitals in Nigeria. Although the knowledge of cardiologists in the management of cardiovascular complications of cancer patients is adequate, referral from General Practitioners is low. The ESC position paper on cardio-oncology is poorly known and utilized by cardiologist in the care of cancer patients with cardiovascular complications with the field of cardio-oncology generally regarded as a new topic in cardiology requiring more information on its dissemination and acceptance. This survey therefore makes obvious the dearth of knowledge regarding cardio-oncology that is prevalent in Nigeria. It is hoped that this will ignite a change in this aspect. There is therefore an urgent need to for all stakeholders to join force together towards the development of cardio-oncology skills and services in Nigeria.

Hyponatremia in a Patient With Cancer

Hyponatremia in a Patient With Cancer

Thrombotic microangiopathy in cancer patients

Thrombotic microangiopathy (TMA) is a rare phenomenon, which is severe pathology based on systemic microvascular thrombosis. TMA is characterized by thrombocytopenia and signs of microangiopathic hemolytic anemia. The review presents a modern data on the pathogenesis of tumor-associated thrombotic microangiopathy, considers the interaction of various effectors related to both tumor growth and metastasis process ― immune system activation, endotheliopathy formation, use of chemotherapeutic agents and targeted therapy in the pathogenesis of various forms of TMA. The interaction between the tumor tissue, hemostasis and immune systems are of the type of cascade of mutual activation, thus leading to the formation of a vicious circle, resulting in damage to endothelium and thrombosis in the microcirculatory channel, that is, the development of TMA. The formation of thromboembolism, which includes tumor tissue in the microvessels of the lungs, contributes to the development of pulmonary tumor thrombotic microangiopathy (PTTM). Сancer patients have higher vWF levels and lower ADAMTS13 levels or/and activity than the general population, often also depending on the stage of cancer: vWF and ADAMTS13 have been shown to be associated with thrombotic complications in cancer patients, and ADAMTS13 shows prognostic potential. Increased expression of complement proteins and/or activation of complement during chemotherapy, infectious and inflammatory complications may also cause TMA development. Pathogenesis of thrombotic microangiopathy also is associated with numerous chemotherapeutic agents, such as mitomycin C, gemcitabine, cisplatin, carboplatin and Bevacizumab, an inhibitor of VEGF. This may be the result of both the direct toxic effect of the drug on endothelium and damage of it by immune complexes caused by expression of the VEGF-antibodies. Usage of number of chemotherapeutic agents, especially anti-VEGF and tyrosine kinase inhibitors, which have a direct toxic effect on endothelium, are associated with the development of TMA. Mechanisms causing the development of TMA are considered as components of the hemostasis system, leading to the development of chronic, long-lasting disorders of the hemostasis system (chronic DIC syndrome) and are associated with high incidence of thrombotic complications.

A Multicenter Study of Romiplostim to Treat Chemotherapy-Induced Thrombocytopenia in Solid Tumors and Lymphoid Malignancies

Introduction : Chemotherapy-induced thrombocytopenia (CIT) is a common complication in cancer patients causing chemotherapy treatment delays, dose reductions, and discontinuation. A major unmet clinical need, there is no FDA-approved agent available to manage CIT. Given this, we developed clinical pathways to treat CIT at 4 large academic hospitals. Data using romiplostim to manage CIT is limited to small single-center studies and case series of solid tumor patients only. We performed the first large multicenter study of romiplostim for CIT, including both solid tumor and non-myeloid hematologic malignancy patients. Methods : We retrospectively collected demographics, cancer and chemotherapy data, romiplostim dosing, weekly platelet counts (Plt), and outcomes of romiplostim support for patients treated on institutional romiplostim CIT pathways from 2009-2019. For solid tumor patients, 2 institutions utilized intracycle dosing (romiplostim administered on average twice monthly on chemotherapy-off weeks) and 2 utilized standard weekly romiplostim dosing, facilitating comparison of dosing strategies. Romiplostim response was defined as a median on-romiplostim Plt of ≥75×109/L and at least 30×109/L higher than baseline. Baseline characteristics were analyzed for predictors of romiplostim non-response using multivariate logistic regression. Wilcoxon signed-rank and Mann-Whitney U tests compared paired and unpaired groups and Chi square and Fisher's exact tests compared categorical outcomes. Results : 173 patients (153 solid tumor, 20 lymphoid malignancy) were treated for CIT with romiplostim to facilitate ongoing chemotherapy administration, with 170 (98%) receiving a median (range) of 4 (1-36) additional chemotherapy cycles over 10 (2-125) weeks of romiplostim support. A total of 61.3 patient-years of romiplostim treatment of CIT were analyzed for effectiveness and safety. Table 1 lists baseline patient characteristics and Table 2 details chemotherapy regimens precipitating CIT and supported on romiplostim. Median per-patient Plt on romiplostim was significantly higher than baseline (all patients, 112×109/L vs. 54×109/L, P&amp;lt;0.001; solid tumor patients, 116×109/L vs. 60×109/L, P&amp;lt;0.001), Figure 1. Median romiplostim starting dose was 3 µg/kg/week, which was also the median optimized romiplostim dose (dose achieving Plt &amp;gt;100×109/L). While on romiplostim, bleeding occurred in 7.5% of patients and venous thromboembolism occurred in 4.6% (at Plt 65-306×109/L). Compared with intracycle romiplostim dosing, weekly romiplostim dosing resulted in higher median Plt (Figure 2) and fewer chemotherapy delays/dose reductions with no difference in bleeding or thrombotic events (Table 3). Characteristics of solid tumor patients predicting non-response to romiplostim per multivariate regression included biopsy-proven bone marrow invasion by tumor (P&amp;lt;0.001), prior pelvic irradiation (P=0.029), and prior temozolomide (P=0.031) (Figure 3), with only 23%, 20%, and 46% of patients, respectively, achieving a romiplostim response compared with 82% of all other solid tumor patients. Plt improvement with romiplostim was modest in patients with myeloma (N=7, median per-patient Plt 39×109/L with romiplostim vs. 19×109/L at baseline, P=0.078) and aggressive lymphoma (N=13, 47×109/L with romiplostim vs. 23×109/L at baseline, P=0.033), Figure 3, with only 35% receiving more than 1 additional chemotherapy cycle on romiplostim. All myeloma and lymphoma patients were dosed weekly and had extensive bone marrow involvement by malignancy. Conclusions : We present results of romiplostim treatment of CIT in a large cohort of 173 cancer patients, including lymphoid malignancies. Dosing strategies were compared and predictors of non-response were evaluated. Romiplostim was highly effective in solid tumor patients with CIT, allowing chemotherapy administration. Bleeding and thrombosis rates were similar to the general cancer patient population. Both weekly and intracycle dosing were effective and equally safe, but weekly dosing maintained higher Plt overall and higher Plt nadirs with fewer chemotherapy dose reductions or treatment delays. Bone marrow invasion, pelvic irradiation, and prior temozolomide predicted romiplostim non-response. Romiplostim had modest effectiveness to manage CIT in lymphoid malignancy patients with underlying bone marrow involvement. Disclosures Al-Samkari: Moderna: Consultancy. Parnes:Sunovion: Consultancy, Other: Safety monitoring board; Hoffman LaRoche: Research Funding; Genentech: Research Funding; Shire: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees; Geron Corporation: Other: owning stock . Connors:Portola: Other: scientific ad boards; Abbott: Consultancy; Bristol Myer-Squibb: Consultancy, Other: Scientific Ad boards; Eli Lilly: Consultancy. Kuter:Up-to-Date: Consultancy, Honoraria, Patents &amp; Royalties: 3 Up-to-Date chapters; Shinogi: Consultancy, Honoraria; Rigel: Consultancy, Honoraria, Research Funding; Zafgen: Consultancy, Honoraria; Platelet Disorder Support Association: Consultancy, Honoraria; UCB: Consultancy, Honoraria; Takeda (Bioverativ): Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria; Momenta: Consultancy, Honoraria; Merck Sharp Dohme: Consultancy, Honoraria; Actelion (Syntimmune): Consultancy, Honoraria, Research Funding; Genzyme: Consultancy, Honoraria; Principia: Consultancy, Honoraria, Research Funding; Protalex: Consultancy, Honoraria, Research Funding; Protalix: Consultancy, Honoraria; Alnylam: Consultancy, Honoraria, Research Funding; Argenx: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb (BMS): Consultancy, Honoraria, Research Funding; Caremark: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Kyowa-Kirin: Consultancy, Honoraria; Agios: Consultancy, Honoraria, Research Funding; Dova: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Shire: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Kezar: Research Funding. OffLabel Disclosure: Off-label use of the thrombopoietin receptor agonist romiplostim to treat chemotherapy-induced thrombocytopenia is discussed.

Modulations of probiotics on gut microbiota in a 5-fluorouracil-induced mouse model of mucositis.

Intestinal mucositis remained one of the most deleterious complications in cancer patients undergoing chemotherapy. 5-FU treatment was reported to affect the abundance of gut microbiota and cause mucositis, which might be ameliorated by probiotics. We investigate the potential changes of 5-FU treatment and the modulations of probiotics on gut microbiota in a mouse model. Male BALB/c mice received either 5-FU or saline (S). They were separated and fed saline, Lactobacillus casei variety rhamnosus (Lcr) and Lactobacillus reuteri DSM 17938 (BG). Lcr and BG were simultaneously administered with 5-FU for 5days. Stool specimens were collected for DNA extraction and pyrosequenced for bioinformatic analysis. Fecal microbial communities were obviously diverse. Bacteroides and Bacteroidaceae were the most abundant microbiota in FU.BG group while S24_7 was the most in S.S group. At phylum and class levels, abundances of Betaproteobacteria, Erysipelotrichi, Gammaproteobacteria, and Verrucomicrobia were significantly increased in the FU groups. Probiotics supplementation did increase the abundances of Enterobacteriales and Turicibacterales. We demonstrated that probiotics did modulate the abundance and diversity of gut microbiota. Bacterial motility proteins were found enriched and upregulated in the S.BG group. No mortality was noted. No bacterial translocation was found in spleen and blood among the six groups. Gut microbiota of mice undergoing chemotherapy exhibited a distinct disruption in bacterial composition. Probiotic did modulate the abundance and diversity of gut microbiota. This is the first study to analyze the effects and safety of Lactobacillus strains on 5-FU-induced mucositis systematically and assess changes in the intestinal microbiota after probiotic intervention.

Biomarker Assessment of Venous Thromboembolism in Cancer Patients Receiving Checkpoint Blockade

Abstract Introduction Immuno-oncology shows significant promise in the treatment of malignancy but is associated with a variety of immune-related adverse events. We previously reported that venous thromboembolism (VTE) occurred in over 20% of patients treated with checkpoint blockade. We therefore have attempted to identify biomarkers/risk factors for VTE in this population that might provide a means to target prophylactic anticoagulant therapy to individuals at highest risk for this complication. Methods We used a database of 1,686 patients who received any of six approved immunotherapies (ipilimumab, nivolumab, pembrolizumab, atezolizumab, avelumab or durvalumab) between July 2015 and December 2017 to identify patients with VTE events including deep venous thrombosis (DVT), pulmonary embolism (PE) and visceral vein thrombosis (VVT). For biomarker/risk factors assessment, we defined a subcohort of cancer patients with (n=14) or without (n=10) VTE after receiving immunotherapy that had consented to blood and data collection in compliance with guidelines approved by the Cleveland Clinic institutional review board. Age matched healthy controls (n = 9) were also included in the analysis. Phenotyping of myeloid-derived suppressor cells (MDSC) was performed on fresh peripheral blood samples following isolation of peripheral blood mononuclear cells (PBMC) and flow cytometry. We measured 1) total MDSC (CD33+HLADR−), and within that population, 2) monocytic M-MDSC (CD14+CD15−), 3) polymorphonuclear/granulocytic PMN-MDSC (CD14−CD15+), 4) immature I-MDSC (CD14−CD15−), as well as surface expression of PD1 and PDL1. Analysis of soluble plasma biomarkers was performed in parallel using the validated Meso Scale Discovery V-PLEX Human Biomarker 54-Plex assay. Results The study group included 7 patients with bladder cancer, 7 with melanoma, 6 with renal cell carcinoma, and 4 with lung cancer. Total MDSC levels in all cancer patients receiving immunotherapy were significantly higher than those of age matched healthy controls (4.278, n=24 vs 1.543, n=9; p = 0.0198). Cancer patients receiving immunotherapy who developed VTE had significantly more PMN-MDSC than patients without VTE (12.59, n=14 vs 1.641, n=10; p = 0.0474). Cancer patients receiving immunotherapy who developed VTE also had elevated levels of pre-immunotherapy total MDSC compared to non-VTE counterparts, though these differences did not achieve statistical significance (4.948, n=14 vs 3.341; NS). Of 54 soluble plasma biomarkers tested, vascular cell adhesion molecule 1 (sVCAM-1) and interleukin 8 (IL-8) levels were also significantly higher in patients who developed VTE compared to those who did not (1.210 vs 0.8955 mg/ml, p= 0.0285; and 221.2 vs 115.0, p= 0.0174, respectively). Conclusions VTE is a common but underappreciated complication in cancer patients receiving immunotherapy. There are no formal risk tools or biomarkers predictive of VTE in cancer patients initiating immunotherapy. We have identified candidate cellular and plasma biomarkers that associate with thrombotic risk in this population and provide potential insight into its pathophysiology. Prospective and mechanistic studies are underway to validate and further expand these findings. Disclosures Khorana: Janssen: Consultancy; Bayer: Consultancy; Pfizer: Consultancy; Sanofi: Consultancy. McCrae:Sanofi Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Rigel Pharmaceutical: Membership on an entity's Board of Directors or advisory committees; Pfizer Pharmaceutical: Membership on an entity's Board of Directors or advisory committees; Dova Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees.

EPID-10. VENOUS THROMBOEMBOLIC EVENTS IN GLIOBLASTOMA PATIENTS: AN EPIDEMIOLOGICAL VIEW

Abstract BACKGROUND Venous thromboembolic events (VTE) are a common complication in cancer patients. Anticoagulant use is the appropriate treatment for acute VTE in cancer, although assumed to be associated with increased risk for bleeding. The population-based relationship of VTE and anticoagulant therapy to survival in glioblastoma patients remains unclear. METHODS Frequency, risk factors, treatment and complications of VTE were assessed in a glioblastoma cohort in the Canton of Zurich, Switzerland (2010 to 2014). Survival data were retrospectively analyzed using the log rank test. RESULTS 248 glioblastoma patients with known isocitrate dehydrogenase (IDH) wildtype status were identified in a 5-year time-frame. Median overall survival (OS) was 12.8 months (95% CI 11.0–14.6), with a median follow up of 60.7 months (95% CI 51.4–70.0). VTE were diagnosed in 35 patients (14.4%; 5 out of 248 patients with no follow-up data on VTE). Median time from diagnosis to VTE was 2.23 months (95% CI 0.6–3.9); 3 patients (8.6%) had a history of VTE. Most patients were on steroids at time of diagnosis of VTE (68.6%), and a Karnofsky Performance Score of less than 70% was documented in 21 patients (60%). Most patients with VTE (88.6%) received therapeutic anticoagulation. Complications, resulting in the cessation of therapeutic anticoagulation, occurred in 11 patients (35.5%), mainly (9 patients, 81.8%) due to intracranial hemorrhage. OS did not differ between patients diagnosed with VTE and those without VTE (p=0.103). Tumor progression was the major cause of death (91.3%); 1.4% of patients died from VTE; 1.9% of the patients suffered unexpected sudden death. CONCLUSION Although VTE were identified in 14.4% of glioblastoma patients, VTE were not the major reason for death. These data do not support the implementation of primary thromboprophylaxis in glioblastoma patients. Prospective clinical trials are needed to examine the association of anticoagulant use with survival in glioblastoma patients.

Spironolactone, a Classic Potassium-Sparing Diuretic, Reduces Survivin Expression and Chemosensitizes Cancer Cells to Non-DNA-Damaging Anticancer Drugs

Spironolactone, a classical diuretic drug, is used to treat tumor-associated complications in cancer patients. Spironolactone was recently reported to exert anti-cancer effects by suppressing DNA damage repair. However, it currently remains unclear whether spironolactone exerts combinational effects with non-DNA-damaging anti-cancer drugs, such as gemcitabine and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Using the cancer cells of lung cancer, pancreatic cancer, and glioblastoma, the combinational effects of spironolactone with gemcitabine and osimertinib, a third-generation EGFR-TKI, were examined in vitro with cell viability assays. To elucidate the underlying mechanisms, we investigated alterations induced in survivin, an anti-apoptotic protein, by spironolactone as well as the chemosensitization effects of the suppression of survivin by YM155, an inhibitor of survivin, and siRNA. We also examined the combinational effects in a mouse xenograft model. The results obtained revealed that spironolactone augmented cell death and the suppression of cell growth by gemcitabine and osimertinib. Spironolactone also reduced the expression of survivin in these cells, and the pharmacological and genetic suppression of survivin sensitized cells to gemcitabine and osimertinib. This combination also significantly suppressed tumor growth without apparent adverse effects in vivo. In conclusion, spironolactone is a safe candidate drug that exerts anti-cancer effects in combination with non-DNA-damaging drugs, such as gemcitabine and osimertinib, most likely through the suppression of survivin.