Clinical Outcomes In Cancer Patients Research Articles

Impact of probiotics use on clinical outcomes of immune checkpoint inhibitors therapy in cancer patients.

Dysbiosis of the gut microbiota can lead to impaired therapeutic effect of immune checkpoint inhibitors (ICIs). This study aimed to investigate the use of probiotics on the clinical outcomes of cancer patients receiving ICIs therapy. PubMed, EMBASE, and the Cochrane Library database were searched to retrieve relevant studies that exploring the relationship between probiotics and the efficacy of ICIs. The primary endpoints included overall survival (OS) and progression-free survival (PFS), evaluated by the hazard rations (HRs) with 95% confidence intervals (CI), and the secondary endpoint was objective response rate (ORR), evaluated by the odd ratio (OR) with a 95% CI. A total of five studies including 1031 patients were eligible for analysis. Our results indicated that the use of probiotics was associated with a superior OS (HR=0.50, 95% CI: 0.30-0.85, p=0.01) and PFS (HR=0.51, 95% CI: 0.42-0.61, p< 0.01), but had no relationship with ORR (OR=2.11, 95%CI: 0.51-8.65, p=0.30) in non-small cell lung cancer (NSCLC) patients. Probiotics were positively correlated with OS and PFS in NSCLC patients administrated with ICIs, but had no relationship with ORR.

Abstract 2544: Preoperative exercise inhibits hepatic metastasis by suppressing PMN-MDSC formation of NETs

Abstract Introduction: Under surgical trauma, the pathological amplification and activation of neutrophils with potent immunosuppressive functions, also known as polymorphonuclear myeloid-derived suppressive cells (PMN-MDSCs), can promote metastasis by forming neutrophil extracellular traps (NETs) that are web-like structures consisting of nuclear DNA, histones, and granule proteins. Preoperative exercise (PEx) reduces postoperative complications with improved clinical outcomes in cancer patients undergoing surgeries. are. Our preliminary data show that PEx suppresses liver ischemia/reperfusion (I/R)-induced colorectal cancer (CRC) liver metastasis. Our recent studies have shown I/R-induced NETs promote liver CRC metastasis by capturing tumor cells and preventing infiltration and cytotoxicity of CD8+ T cells in tumor microenvironment (TME). We hypothesize that PEx remodels the TME by suppressing PMN-MDSCs formation of NETs. Methods: Male mice were subjected to exercise for 4 weeks, before MC38 colorectal cancer cells were injected through portal vein, and then subjected to 70% partial liver warm I/R as surgical stress. The single-cell RNA sequencing (scRNA-seq) was performed on CD45+leukocytes from TME 3 weeks after surgery. Immunofluorescence staining and Western Blot were used to determine NETs formation in the TME. Flow cytometry was used to determine the infiltration of PMN-MDSCs and CD8+ T lymphocytes in the tumors. Results: Our scRNA-seq data reveal that PEx leads to a remarkable transcriptomic shift in most immune cells types, such as PMN-MDSCs, M-MDSCs, T cells, Kupffer cells, B cells, NK and NKT cells, in the TME. PEx decreases the percentages of PMN-MDSCs in the TME and inhibits theNETs formation by PMN-MDSCs. scRNA-seq shows a significant increase of the chemokines CXCL10 in PEx-trained PMN-MDSCs obtained 3 weeks after I/R-induced hepatic metastasis, compared with sedentary controls. In addition, PEx increases the number of CD8+ T lymphocytes infiltrating the TME. Summary: Our study shows that PEx downregulates NETs formation and increases the CXCL10 expression in PMN-MDSCs, thus promoting the recruitment more cytotoxic CD8 T lymphocytes to suppress tumor metastasis. Citation Format: Xiang Cheng, Hongji Zhang, Allan Tsung, Hai Huang. Preoperative exercise inhibits hepatic metastasis by suppressing PMN-MDSC formation of NETs [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 2544.

Proposing a social determinants of health (SDOH) EMR dashboard to improve heath equity in cancer care.

e18548 Background: There are biological differences in the clinical outcomes of Black or Hispanic cancer patients compared with non-Hispanic Whites (NHWs); however minorities have disadvantages in social determinants of health (SDOH) that influence cancer outcomes too. The World Health Organization defines SODH as the conditions in which people are born, grow, live, work, age, and maintains that they are largely responsible for health inequities . Most the oncology professionals do not consider that this issue is necessarily part of their scope of practice and they rely on social workers and others to address these issues, and they are not aware that SDOH can impact clinical outcomes of cancer patients. Methods: Memorial Cancer Institute (MCI) part of the Memorial Healthcare System (MHS) is the 3rd largest Public Health Care System in the country. We found important disparities in immunotherapy outcomes in our MCI minority lung cancer patients ( Raez LE. Research Trends. 2021 Feb (20) 63–74 and Dickson F. JTO Vol. 16 (10) S904–5), some of these are related to SDOH. In order to increase awareness of SDOH and identify the impact of SDOH on cancer outcomes, our MHS value-based care team has been working to incorporate SDOH screening and follow-up as an important part of treatment plan development since 2018. At that time, MHS implemented an SDOH dashboard in our EPIC EMR to show the SDOH areas of risk. In 2021, MHS built a best practice alert in Epic to notify health care providers about SDOH issues that might impact treatment outcomes. Results: MHS has implemented a SDOH dashboard in the EPIC EMR that is accessible and easily noticed by the providers and updated constantly by our social workers and other health professionals screening for SDOH. Providers do not need to do extra work other than to be aware that the best cancer treatment that they are recommending for a patient might not have the desired outcome if some of these 13 SDOH are not considered during the planning phase of treatment. The SDOH dashboard uses color coding to indicate if any SDOH is at risk (red) or not at risk or low risk (green) allowing the provider to easily focus in on areas of concern when SDOH is reviewed. Conclusions: Using an easy to access and easy to read SDOH dashboard in the EMR allows oncology providers to address SDOH in the development of oncology treatment plans which we believe will lead to improved health care outcomes.[Table: see text]

Systematic review and meta-analysis evaluating the impact of antibiotic use on the clinical outcomes of patients with cancer treated with immune checkpoint inhibitors.

2585 Background: In recent years, the gut microbiome has increasingly emerged as influencing the response to immune checkpoint inhibitors (ICIs) and antibiotic (ABX) exposure has repeatedly been shown to impair clinical outcomes of patients suffering from different cancer types and treated with ICIs. We published in 2020 a meta-analysis confirming that ABX use hampered survival of non-small cell lung cancer (NSCLC) patients treated with ICIs. The present study aims to determine whether ABX use also reduces survival of patients receiving ICIs for other cancers. Methods: PubMed and major oncology conferences’ proceedings were systematically searched to identify studies assessing the impact of ABX on the clinical outcomes of cancer patients treated with ICIs. Studies were included when reporting data on Overall Survival (OS), Progression-Free Survival (PFS), Overall Response Rate (ORR) and Progressive Disease Rate (PD), according to ABX exposure. Pooled Hazard Ratios (HRs) for OS and PFS and Odds Ratios (ORs) for ORR and PD were calculated, as well as HRs for OS and PFS according to different cancer types and different ABX exposure time windows (TWs). Results: Overall, 94 independent cohorts were included, representing 26,174 patients suffering from various types of cancer. The pooled HRs for PFS (61 cohorts, 13,224 patients) and OS (88 cohorts, 25,480 patients) were 1.47 [95% Confidence Interval (CI) 1.31-1.66] and 1.66 [95% CI 1.50-1.83], respectively, confirming a significant harmful impact of ABX on patient’ survival, observed across all cancer types (Table). The analyses of OS and PFS based on ABX exposure TWs suggested a stronger deleterious effect of ABX when taken around ICI treatment initiation. The response to treatment among ABX users was also impaired: the pooled ORs for ORR (30 cohorts, 4,590 patients) and PD (33 cohorts, 4,972 patients) were 0.55 [95% CI 0.39-0.77] and 1.97 [95% CI 1.48-2.64], respectively. Conclusions: ABX were shown to impair the clinical outcomes of cancer patients treated with ICIs, regardless of cancer type. [Table: see text]

Quality of life in caregivers of cancer patients in Colombia.

e24000 Background: It is well known that improvements in caregiver quality of life (QOL) could significantly impact the clinical outcome of cancer patients, which is why it is essential to study this population. Caregivers have extensive responsibilities, making them vulnerable to emotional, physical, social, and financial distress. Evaluation of cancer patient caregiver QOL in Latin America and validation of QOL metrics, such as the Caregiver Quality of Life Index-Cancer (CQOLC), has not yet been done in large populations. We sought to evaluate these characteristics in 5 regions in Colombia. Methods: Cancer patients (n = 165) receiving active treatment and their respective adult caregivers were evaluated. Both caregivers and patients completed a sociodemographic survey, along with the CQOLC, which was translated to Colombian Spanish and validated in a pilot cohort. CQOLC is composed of five subcategories with a total max score of 140. Higher scores are associated with better QOL. Internal consistency was determined by Cronbach’s alpha. Results: The patient’s median age was 63 years (58.8% females). The primary cancer diagnoses were breast, cervical, and lung cancer, with a median ECOG-PS of 1. 6.3% of patients did not have a caregiver, and their responses were also evaluated. The median caregiver age was 53 years (range 19-75 years, 60% females). 4.7% of caregivers were unemployed, and 59% reported financial or psychological distress. 93.8% of caregivers were family members, most frequently spouses or children. The median CQOLC score was 90 ± 15.2. The median score for each of the five subcategories “burden,” “disruptiveness,” “positive adaption,” “financial concern,” and “other” were as follows: 2, 3, 3, 3, and 3 (max score of 4). Conclusions: Most patients and caregivers were interested in participating in the study and reported no issues comprehending or answering the questions. This suggests no potential problems adapting the Spanish-translated CQOLC to future studies. Despite most caregivers reporting financial distress and low family income status, their overall CQOLC scores were relatively high compared to developing countries like the USA, potentially due to cross-cultural differences. The higher median score in the “disruptiveness” category suggests that Colombian caregivers feel strongly committed to caregiving and do not feel this activity interferes significantly with their daily life, possibly related to a sense of family responsibility and moral duty. However, the lower median score in the “burden” category indicates that caregivers feel a heavy emotional toll as a result of their caregiving role. Our results can help identify caregiver QOL areas of improvement, where government policies can be implemented to benefit both the caregiver and the patient.Keywords: caregiver burden, quality of life, Colombia, validation, CQOLC, cancer patients

Assessing the impact of hypercalcemia of malignancy on clinical outcomes in cancer patients admitted with acute pancreatitis.

e24049 Background: Hypercalcemia of malignancy is a well-recognized complication in cancer. Hypercalcemia itself is one of the etiologies of acute pancreatitis. Empiric data on how presence of both these entities affect hospitalization outcomes in cancer patients is lacking. We studied 5 common cancers - Lung cancer, multiple myeloma, diffuse large B-cell lymphoma, renal cell cancer and head &amp; neck cancers with known hypercalcemia of malignancy and studied the outcomes if they developed acute pancreatitis versus not. Methods: Healthcare Cost and Utilization Project National Inpatient Sample (HCUP-NIS) 2016 – 2018 was queried to identify adult patients with known hypercalcemia of malignancy and any of the 5 cancers stated above. From this cohort we identified patients admitted with a principal diagnosis of acute pancreatitis. The frequency of various etiologies of acute pancreatitis in the defined population was assessed. Primary outcomes assessed were mortality, length of stay (LOS), and total hospitalization charges (THC). Secondary outcomes included diagnosis of septic shock, acute kidney injury (AKI), and acute respiratory failure (ARF). Statistics were performed using multivariate linear and logistic regression. Results: There were a total of 44,030 adult patient hospitalizations with history of hypercalcemia of malignancy and one of the 5 cancers of which 4,195 hospitalizations were for acute pancreatitis. The most common etiology for acute pancreatitis was idiopathic (69.4%), followed by biliary pancreatitis (15.7%), alcohol-associated pancreatitis (7.75%) and drug-induced pancreatitis (7.15%). The incidence of acute pancreatitis was higher in the hypercalcemia of malignancy group than those without (0.36% vs 0.28%). Hypercalcemia of malignancy group had significantly increased odds of mortality during admission for acute pancreatitis (15.63% vs 3.48%, aOR: 3.48, p = 0.043) and significantly higher THC ($122,184 vs $49,223, adjusted difference of $69,974.59, p = 0.049). There was a trend towards an increased LOS among patients with hypercalcemia of malignancy (10.7 vs 5.5 days), but it was not statistically significant (p = 0.069). Hypercalcemia of malignancy was also associated with an increased odds of AKI, 53.13% vs 16.85% (aOR: 6.15, p &lt; 0.001). Other outcomes of septic shock and ARF were similar between groups. Conclusions: Despite the high prevalence of hypercalcemia of malignancy in certain at-risk cancer groups, the most common etiology of acute pancreatitis is idiopathic. The history of hypercalcemia of malignancy in cancer patients with acute pancreatitis was associated with a 3-fold increased odds of death, higher odds of AKI and a significant increase in THC. Cancer patients with history of hypercalcemia presenting with acute pancreatitis may need more aggressive management to prevent worse outcomes than patients without history of hypercalcemia.

Characteristics and outcomes of COVID-19 in adult cancer patients: Tertiary cancer center experience.

e13601 Background: The COVID-19 pandemic has led to deteriorated outcomes among immunocompromised patients, significantly impacting cancer patients. However, little is known about the impact of the COVID-19 pandemic on cancer patients in low and middle-income countries. Therefore, we sought to investigate the characteristics and clinical outcomes of cancer patients with COVID-19 treated at a single institution. Methods: A retrospective chart review was performed for cancer patients treated at King Hussein Cancer Center. Patients who were diagnosed with laboratory-confirmed SARS-CoV-2 infection by Real-time Polymerase chain reaction test between April 2020 and October 2020 were identified. Results: Overall, 327 COVID-19-infected cancer patients were included. At the time of COVID-19 diagnosis, the median age was 55 years (range, 18-87 years), 146 patients (45%) were males. The most common neoplasms were breast cancer (n = 90, 27.5%), gastrointestinal cancers (n = 60, 18.3%), and lymphoma (n = 36, 11%). The majority of patients had comorbidities (n = 200, 61%), of which hypertension and diabetes mellitus were the most common. Testing reason was presence of symptoms in 183 (56%) patients, previous exposure in 10 (3.1%), and before elective procedure in 142 (43.4%). 118 patients (56.5%) were hospitalized and 18 patients (5.5%) required admission to the intensive care unit (ICU). At the time of the last follow-up, 76% (n = 249) remained alive, and 24% (n = 78) died, among which death was considered to be COVID related in 41 (52.5% of deaths). Mortality was significantly increased in patients with comorbidities (29%, vs 15.7 %; p = 0.008), the use of cardiac medications (34.3% vs. 18.1%; p = 0.001), active cancer status vs. remission (28.2% vs 11.6% p = 0.002), receiving chemotherapy in the last four weeks (27.6% vs 16.4%, p = 0.028), and when testing reason was the presence of symptoms vs exposure and elective (37.7% vs. 10% and 7.7% p = &lt; 0.001) respectively. Chemotherapy was delayed in 109 (33.4%) patients and permanently discontinued in 57 (17.5%) patients. Among patients required hospitalization and needed ICU admission, mortality rates were 55.1% and 88.9% respectively. Conclusions: COVID-19 infection is associated with significant mortality and negatively affects treatment plans in cancer patients. A follow-up study will be needed to evaluate the effect of vaccination on the outcomes.

A Novel Diagnostic and Therapeutic Strategy for Cancer Patients by Integrating Chinese Medicine Syndrome Differentiation and Precision Medicine.

Applying Chinese medicine (CM) is an important strategy for malignant tumor treatment in China. One of the significant characteristics of CM is to treat diseases based on syndrome differentiation. For Western medicine, it is of important clinical significance to formulate guidelines for the diagnosis and treatment of cancer patients based on the characteristics of disease differentiation. In Chinese clinical practice, the combination of disease differentiation and syndrome differentiation is an important feature for cancer treatment in the past. Currently, molecular profiling and genomic analysis-based precision medicine optimizes the anticancer drug design and holds the greatest success in treating cancer patients. Therefore, we want to know which populations of cancer patients can benefit more from CM treatment if the theory of precision medicine is applied to CM clinical practice. So, we developed a novel diagnostic and therapeutic strategy “disease-syndrome differentiation-genomic profiling-prescriptions” for cancer patients by CM syndrome differentiation and precision medicine. As a result, this strategy has greatly enhanced the anti-tumor efficacy of CM and improved clinical outcomes for cancer patients with some gene mutations. Our idea will hopefully establish a novel approach for the inheritance and innovation of CM.

Sperm Autoantigenic Protein 17 Predicts the Prognosis and the Immunotherapy Response of Cancers: A Pan-Cancer Analysis.

BackgroundSperm autoantigen protein 17 (SPA17) is a highly conserved mammalian protein that participates in the acrosome reaction during fertilization and is a recently reported member of the cancer-testicular antigen (CTA) family. It has been reported that the SPA17 expression is limited in adult somatic tissues and re-expressed in tumor tissues. Recently, studies have found that SPA17 regulates the progression of various cancers, but its role in cancer immunotherapy is not clear.MethodsThe pan-cancer and normal tissue transcriptional data were acquired from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) datasets. We explored the SPA17 pan-cancer genomic alteration analysis in the cBioPortal webtool. The Human Protein Atlas (HPA) and ComPPI websites were used to mine the SPA17 protein information. We performed a western blotting assay to validate the upregulated SPA17 expression in clinical glioblastoma (GBM) samples. The univariate Cox regression and Kaplan–Meier method were used to assess the prognostic role of SPA17 in pan-cancer. Gene Set Enrichment Analysis (GSEA) was used to search the associated cancer hallmarks with SPA17 expression in each cancer type. TIMER2.0 was the main platform to investigate the immune cell infiltrations related to SPA17 in pan-cancer. The associations between SPA17 and immunotherapy biomarkers were performed by Spearman correlation analysis. The drug sensitivity information from the Connectivity Map (CMap) dataset was downloaded to perform SAP17-specific inhibitor sensitivity analysis.FindingsSPA17 was aberrantly expressed in most cancer types and exhibited prognosis predictive ability in various cancers. In addition, our results also show that SPA17 was significantly correlated with immune-activated hallmarks (including pathways and biological processes), immune cell infiltrations, and immunoregulator expressions. The most exciting finding was that SPA17 could significantly predict anti-PDL1 and anti-PD1 therapy responses in cancer patients. Finally, specific inhibitors, like irinotecan and puromycin, which correlate with SPA17 expression in different cancer types, were also screened using Connectivity Map (CMap).ConclusionsOur results reveal that SPA17 was abnormally expressed in cancer tissues, and this expression pattern could be associated with immune cell infiltrations in tumor microenvironments. Clinically, SPA17 not only acted as a potent prognostic factor to predict the clinical outcomes of cancer patients but was also a promising immunotherapy predictive biomarker for cancer patients treated with immune-checkpoint inhibitors (ICIs).

C-11 | Clinical Outcomes of Cancer Patients Hospitalized with Acute Pulmonary Embolism

There is paucity of data about the optimal treatment of acute pulmonary embolism (PE) in patients with malignancy. The objective of this study was to compare outcomes of catheter-directed thrombolysis (CDT), Systemic thrombolysis (ST), and no intervention (NI) in patients with cancer and hospitalized with acute PE.

Stratification by Race Reveals Disparate Vascular Toxicity in Response to Anti‐Cancer Therapies

IntroductionCardiovascular toxicity is the primary reason for halting anti‐cancer therapy (CTx) or limiting the dose, and cardiovascular side effects of CTx represent a major clinical problem with implications for survival and quality of life. Ongoing work in our laboratory suggests that CTx induces microvascular endothelial dysfunction, which is a well‐established predictor of future CV events. CV disease in general and CTx‐induced adverse events are significantly more prevalent in Black patients (B) relative to non‐Hispanic White patients (NHW). Despite clinical evidence of these health disparities, little to no data exist to explain the underlying causes. Therefore, we tested the novel hypothesis that CTx‐induced microvascular dysfunction is augmented in B, which may explain the increase in cardiotoxic events in this population compared to NHW.MethodsFresh human tissues were obtained as de‐identified surgical discard specimens. Peripheral adipose arterioles (100–200 µm) from healthy B and NHW were incubated ex vivowith the CTx agents, doxorubicin (Dox), trastuzumab (TZM), or paclitaxel (PTX) for 16–20 h and used for isolated arteriole preparations. Endothelium‐dependent vasodilation in response to flow (Flow‐Mediated Dilation, FMD; 5–100 cmH2O pressure gradient) or acetylcholine (ACh; 10−9 to 10−5 M) and smooth muscle‐dependent dilation to papaverine (100 µM) were evaluated. Data are presented as % max. diameter ± SEM, N. Statistical significance was established with two‐way ANOVA RM.ResultsUnder control conditions, there was no difference in microvascular FMD in healthy B (ACh: 89.8±4.0%, n=5; 85.8±1.8%, n=6) vs. NHW (ACh: 86.2±3.2%, n=6; 78.7±5.9%, n=8). Ex vivo exposure to Dox impaired endothelial function in arterioles from both B and NHW (ACh: 45.0±10.5%, n=4 and 34.2±9.8%, n=7; FMD: Figure 1A). TZM impaired endothelial function to a greater extent in arterioles from B (ACh: 36.1±7.1%, n=3; FMD: Figure 1B) compared to NHW (ACh: 44.4±8.6%, n=8; FMD: Figure 1B). Interestingly, PTX did not affect endothelial function in NHW (ACh: 91.5±1.6%, n=4; FMD: Figure 1C), but impaired endothelial function in arterioles from B (ACh: 54.7±12.9%, n=3; FMD: Figure 1C). Max dilator capacity to the endothelium‐independent dilator papaverine was not changed in either group (not shown).ConclusionOur findings reveal disparate effects of CTx agents on microvascular endothelial function from B and NHW patients. This raises the possibility that microvascular dysfunction may contribute to the known disparities in adverse CV clinical outcomes of cancer patients and potentially other CV pathologies (e.g., disparities in adverse events associated with PTX‐eluting stents.) Future work should differentiate between biological/genetic vs. social/environmental contribution to observed microvascular responses to CTx.

De novo Creation and Assessment of a Prognostic Fat-Age-Inflammation Index "FAIN" in Patients With Cancer: A Multicenter Cohort Study.

Background and AimsMalnutrition is highly prevalent and is related to multiple impaired clinical outcomes in cancer patients. This study aimed to de novo create an objective, nutrition-related index specially for prognostic purposes in oncology populations.MethodsWe performed a multicenter cohort study including 14,134 cancer patients. The prognostic impact for each baseline characteristic was estimated by calculating Harrell's C-index. The optimal parameters reflecting the nutritional and inflammatory impact on patients' overall survival were selected to develop the fat-age-inflammation (FAIN) index. The associations of the FAIN with the nutritional status, physical performance, quality of life, short-term outcomes and mortality of patients were comprehensively evaluated. Independent external validation was performed to further assess the prognostic value of the FAIN.ResultsThe study enrolled 7,468 men and 6,666 women with a median age of 57 years and a median follow-up of 42 months. The FAIN index was defined as: (triceps skinfold thickness + albumin) / [age + 5 × (neutrophil count/lymphocyte count)]. There were significant associations of the FAIN with the nutritional status, physical performance, quality of life and short-term outcomes. The FAIN also showed better discrimination performance than the Nutritional Risk Index, the Prognostic Nutritional Index and the Controlling Nutritional Status index (all P < 0.05). In multivariable-adjusted models, the FAIN was independently associated with a reduced death hazard both as a continuous variable (HR = 0.57, 95%CI = 0.47–0.68) and per one standard deviation (HR = 0.83, 95%CI = 0.78–0.88). External validation in a multicenter lung cancer cohort (n = 227) further confirmed the prognostic value of the FAIN.ConclusionsThis study created and assessed the prognostic FAIN index, which might act as a feasible option to monitor the nutritional status and help develop intervention strategies to optimize the survival outcomes of cancer patients.

Effect of Educational Program for Nurses on Clinical Outcomes of Cancer patients with Metastatic Spinal Cord Compression

Effect of Educational Program for Nurses on Clinical Outcomes of Cancer patients with Metastatic Spinal Cord Compression

Targeting Epithelial-to-Mesenchymal Transition in Radioresistance: Crosslinked Mechanisms and Strategies.

Radiotherapy exerts a crucial role in curing cancer, however, its treatment efficiency is mostly limited due to the presence of radioresistance. Epithelial-to-mesenchymal transition (EMT) is a biological process that endows the cancer cells with invasive and metastatic properties, as well as radioresistance. Many potential mechanisms of EMT-related radioresistance being reported have broaden our cognition, and hint us the importance of an overall understanding of the relationship between EMT and radioresistance. This review focuses on the recent progresses involved in EMT-related mechanisms in regulating radioresistance, irradiation-mediated EMT program, and the intervention strategies to increase tumor radiosensitivity, in order to improve radiotherapy efficiency and clinical outcomes of cancer patients.

Characteristics and Outcomes of Intracranial Hemorrhage in Cancer Patients Visiting the Emergency Department.

Intracranial hemorrhage (ICH) is a dreaded complication of both cancer and its treatment. To evaluate the characteristics and clinical outcomes of cancer patients with ICH, we identified all patients with ICH who visited The University of Texas MD Anderson Cancer Center emergency department between 1 September 2006 and 16 February 2016. Clinical and radiologic data were collected and compared. Logistic regression analyses were used to determine the association between clinical variables and various outcomes. During the period studied, 704 confirmed acute ICH cases were identified. In-hospital, 7-day, and 30-day mortality rates were 15.1, 11.4, and 25.6%, respectively. Hypertension was most predictive of intensive care unit admission (OR = 1.52, 95% CI = 1.09–2.12, p = 0.013). Low platelet count was associated with both in-hospital mortality (OR = 0.96, 95% CI = 0.94–0.99, p = 0.008) and 30-day mortality (OR = 0.98, 95% CI = 0.96–1.00, p = 0.016). Radiologic findings, especially herniation and hydrocephalus, were strong predictors of short-term mortality. Among known risk factors of ICH, those most helpful in predicting cancer patient outcomes were hypertension, low platelet count, and the presence of hydrocephalus or herniation. Understanding how the clinical presentation, risk factors, and imaging findings correlate with patient morbidity and mortality is helpful in guiding the diagnostic evaluation and aggressiveness of care for ICH in cancer patients.

Predicting clinical outcomes of cancer patients with a p53 deficiency gene signature

The tumor suppressor p53, encoded by the TP53 gene, is mutated or nullified in nearly 50% of human cancers. It has long been debated whether TP53 mutations can be utilized as a biomarker to predict clinical outcomes of cancer patients. In this study, we applied computational methods to calculate p53 deficiency scores (PDSs) that reflect the inactivation of the p53 pathway, instead of TP53 mutation status. Compared to TP53 mutation status, the p53 deficiency gene signature is a powerful predictor of overall survival and drug sensitivity in a variety of cancer types and treatments. Interestingly, the PDSs predicted clinical outcomes more accurately than drug sensitivity in cell lines, suggesting that tumor heterogeneity and/or tumor microenvironment may play an important role in predicting clinical outcomes using p53 deficiency gene signatures.

Co-Expression of miR155 or LSD1 shRNA Increases the Anti-Tumor Functions of CD19 CAR-T Cells.

Chimeric antigen receptor (CAR) T cells targeting CD19 antigen have produced remarkable clinical outcomes for cancer patients. However, identifying measures to enhance effector function remains one of the most challenging issues in CD19-targeted immunotherapy. Here, we report a novel approach in which a microRNA (miRNA) or short-hairpin RNA (shRNA) cassette was integrated into CAR-expressing retroviral vectors. Using this system, we generated anti-CD19 CAR-T cells co-expressing miR155 or LSD1 shRNA and found that anti-CD19 CAR-T cells with miR155 upregulation or LSD1 downregulation exhibited increased anti-tumor functions in vitro and in vivo. Transcriptional profiling analysis by RNA sequencing revealed the targets of miR155 and LSD1 in anti-CD19 CAR-T cells. Our experiments indicated that introduction of miRNA or shRNA expression into anti-CD19 CAR T-cells might be an effective strategy to improve the anti-tumor effects of CAR-T cell therapy.

Characteristics and Clinical Outcomes of Cancer Patients who Developed Constrictive Physiology After Pericardiocentesis.

This study aimed to identify the characteristics and clinical outcomes of cancer patients who developed constrictive physiology (CP) after percutaneous pericardiocentesis. One-hundred thirty-three cancer patients who underwent pericardiocentesis were divided into 2 groups according to follow-up echocardiography (CP vs. non-CP). The clinical history, imaging findings, and laboratory results, and overall survival were compared. CP developed in 49 (36.8%) patients after pericardiocentesis. The CP group had a more frequent history of radiation therapy. Pericardial enhancement and malignant masses abutting the pericardium were more frequently observed in the CP group. Fever and ST segment elevation were more frequent in the CP group, with higher C-reactive protein levels (6.6±4.3mg/dL vs. 3.3±2.5mg/dL, p<0.001). Pericardial fluid leukocytes counts were significantly higher, and positive cytology was more frequent in the CP group. In baseline echocardiography before pericardiocentesis, medial e' velocity was significantly higher in the CP group (8.6±2.1cm/s vs. 6.5±2.3cm/s, p<0.001), and respirophasic ventricular septal shift, prominent expiratory hepatic venous flow reversal, pericardial adhesion, and loculated pericardial fluid were also more frequent. The risk of all-cause death was significantly high in the CP group (hazard ratio, 1.53; 95% confidence interval,1.10-2.13; p=0.005). CP frequently develops after pericardiocentesis, and it is associated with poor survival in cancer patients. Several clinical signs, imaging, and laboratory findings suggestive of pericardial inflammation and/or direct malignant pericardial invasion are frequently observed and could be used as predictors of CP development.

The Early Detection of Circulating Tumor Cells Using Telomerase-Selective Replicating Adenovirus in Pancreatic Cancer Patient

Circulating tumor cells (CTCs) have a crucial role in the clinical outcome of cancer patients. Detection of pancreatic cancer using an antibody against epithelial cell adhesion molecule (EpCAM) in captured CTCs has low sensitivity; the loss of epithelial markers leads to underestimation of CTCs with mesenchymal phenotype. We propose a new approach for detection of viable CTCs, including those with epithelial-mesenchymal transition status (EMT-CTCs), using the new telomerase- specific replication-selective adenovirus (OBP-401), TelomeScan.

Modulating undruggable targets to overcome cancer therapy resistance

Many cancer patients frequently fail to respond to anti-cancer treatment due to therapy resistance which is the major obstacle towards curative cancer treatment. Therefore, identification of the molecular mechanisms underlying resistance is of paramount clinical and economic importance. The advent of targeted therapies based on a molecular understanding of cancer could serve as a model for strategies to overcome drug resistance. Accordingly, the identification and validation of proteins critically involved in resistance mechanisms represent a path towards innovative therapeutic strategies to improve the clinical outcome of cancer patients. In this review, we discuss emerging targets, small molecule therapeutics and drug delivery strategies to overcome therapy resistance. We focus on rational treatment strategies based on transcription factors, pseudokinases, nuclear export receptors and immunogenic cell death strategy. Historically, unliganded transcription factors and pseudokinases were considered undruggable while blocking the nuclear export e.g., through inhibition of the nuclear export receptor CRM1 was predicted as highly toxic. Recent success inhibiting Gli-1, HIF-1α, HIF-2α and reactivating the tumor suppressor transcription factors p53 and FOXO illustrates the feasibility and power of this targeting approach. Similarly, progress has been made in modulating the activity of pseudokinase proteins implicated in therapy resistance including members of the Tribbles protein family. On the other hand, the recent clinical approval of Selinexor, a specific inhibitor of CRM-1, a protein that mediates the transport of cargos with leucine-rich nuclear export signals and known to be a driver of drug resistance, represents the proof-of-concept for inhibiting the nuclear export as a feasible strategy to overcome therapy resistance. The ever-growing capacity to target resistance mechanisms with judiciously selected small molecules, some of which are being formulated within smart nanoparticles, will pave the way towards the improvement of the clinical outcome and realize the full potential of targeted therapies and immunotherapies.