scholarly journals Hyperglycemia During Childhood Cancer Therapy: Incidence, Implications, and Impact on Outcomes

2019 ◽  
Vol 2019 (54) ◽  
pp. 132-138 ◽  
Author(s):  
Allison Grimes ◽  
Ashraf Mohamed ◽  
Jenna Sopfe ◽  
Rachel Hill ◽  
Jane Lynch
Keyword(s):  
Risk Factors ◽  
Cancer Therapy ◽  
Adverse Effects ◽  
Cancer Treatment ◽  
Childhood Cancer ◽  
Pediatric Cancer ◽  
Immune Checkpoint Inhibitors ◽  
Systematic Approach ◽  
Checkpoint Inhibitors ◽  
Limited Data

Abstract Hyperglycemia is a known complication of therapies used in the treatment of childhood cancer, particularly glucocorticoids and asparaginase. It has been linked to increased infection and reduced survival. With more limited data on hyperglycemia during childhood cancer treatment compared with adult cancer, impact on outcomes is less clear in this population. As additional glycemic-altering cancer agents including immune checkpoint inhibitors and targeted therapies make their way into pediatric cancer treatment, there is a more pressing need to better understand the mechanisms, risk factors, and adverse effects of hyperglycemia on the child with cancer. Thus, we utilized a systematic approach to review the current understanding of the incidence, implications, and outcomes of hyperglycemia during childhood cancer therapy.

scholarly journals Myocarditis Surveillance With High-Sensitivity Troponin I During Cancer Treatment With Immune Checkpoint Inhibitors

2021 ◽  
Vol 3 (1) ◽  
pp. 137-139
Author(s):  
Sarah Waliany ◽  
Joel W. Neal ◽  
Sunil Reddy ◽  
Heather Wakelee ◽  
Sumit A. Shah ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Troponin I ◽  
Checkpoint Inhibitors ◽  
High Sensitivity ◽  
High Sensitivity Troponin

scholarly journals Immune-Related Adverse Events (irAE) in Cancer Immune Checkpoint Inhibitors (ICI) and Survival Outcomes Correlation: To Rechallenge or Not?

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 989
Author(s):  
Heidar J. Albandar ◽  
Jacob Fuqua ◽  
Jasim M. Albandar ◽  
Salahuddin Safi ◽  
Samuel A. Merrill ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Survival Outcomes ◽  
Limited Data ◽  
Risk Of Death ◽  
Survival Difference ◽  
Histopathologic Diagnosis ◽  
Cancer Types

Introduction: There is growing recognition of immune related adverse events (irAEs) from immune checkpoint therapies being correlated with treatment outcomes in certain malignancies. There are currently limited data or consensus to guide management of irAEs with regards to treatment rechallenge. Methods: We conducted a retrospective analysis with an IRB-approved protocol of adult patients seen at the WVU Cancer Institute between 2011–2019 with a histopathologic diagnosis of active cancers and were treated with immune checkpoint inhibitors (ICI) therapy. Results: Demographics were similar between the ICI interrupted irAE groups within cancer types. Overall, out of 548 patients who received ICI reviewed, there were 133 cases of ≥1 irAE found of any grade. Being treated with anti-CTLA-4 inhibitor ICI was associated with lower risk of death compared to anti-PD-1 ICI. The overall survival difference observed for irAE positive patients, between rechallenged (37.8 months, reinitiated with/without interruption; 38.6 months, reinitiated after interruption) and interrupted/non-reinitiated (i.e., discontinued) groups (24.9 months) was not statistically significant, with a numerical trend favoring the former. Conclusions: Our exploratory study did not identify significantly different survival outcomes among the Appalachian West Virginia adult cancer patients treated with ICI who developed irAE and had treatment reinitiated after interruption, when compared with those not reinitiated.

Immune checkpoint inhibitors: Significant advancements in non–small cell lung cancer treatment

2021 ◽  
Author(s):  
Ashley E Glode ◽  
Megan B May
Keyword(s):  
Lung Cancer ◽  
Cancer Treatment ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Novel Therapies ◽  
Small Cell Lung

Abstract Purpose This article explores the efficacy, toxicity, place in therapy, and considerations for use of recently approved immune checkpoint inhibitors (ICIs) in the treatment of non–small cell lung cancer (NSCLC). Summary Lung cancer is the leading cause of cancer mortality in the United States and is responsible for more cancer-related deaths than breast, prostate, and colorectal cancer combined. The landscape for lung cancer treatment is evolving with the approval of new and exciting novel therapies. Within the last decade numerous ICIs have been approved for use in the management of the most common subtype of lung cancer, NSCLC. The ICI agents currently approved by the Food and Drug Administration (FDA) for use in NSCLC include ipilimumab, pembrolizumab, nivolumab, durvalumab, and atezolizumab. These agents are approved for specific indications; therefore, they are not interchangeable. This review focuses on the landmark trials that led to each FDA-approved indication, as well as common toxicities seen with use of these agents. It also discusses the use of ICIs in special populations and unique considerations prior to initiation of treatment with these novel therapies in a patient with NSCLC. Conclusion ICIs can provide a breakthrough treatment option for the management of NSCLC and are rapidly being adopted into clinical practice. It is important to be familiar with appropriate selection of an ICI therapy option for each patient based on approved indication, unique considerations, and anticipated toxicities.

Genetic and treatment risks for diabetes mellitus (DM) in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS) and St. Jude Lifetime (SJLIFE) cohorts.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10014-10014
Author(s):  
Melissa A. Richard ◽  
Sogol Mostoufi-Moab ◽  
Nisha Rathore ◽  
Austin L. Brown ◽  
Stephen J. Chanock ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cancer Survivors ◽  
Cancer Treatment ◽  
Childhood Cancer ◽  
Regulatory Region ◽  
Childhood Cancer Survivors ◽  
Population Based ◽  
European Ancestry ◽  
Radiation Group ◽  
Increased Risk

10014 Background: Childhood cancer survivors face increased risk for DM, a polygenic trait also attributable to cancer treatment exposures, particularly abdominal radiation. We aimed to characterize the role of genetic and treatment risk factors for DM among two large cohorts of childhood cancer survivors. Methods: We performed a nested case-control genome-wide association study for DM managed with oral medications in the original CCSS cohort (diagnosed 1970-1986). Logistic regression was conducted in the total sample (N = 5083) and stratified by 1) European ancestry (EA) and 2) abdominal radiation. Replication of suggestive variants (P < 1×10-7) using Fisher’s exact test was performed in independent cohorts: i) CCSS expansion diagnosed 1987-1999 (N = 2588) and ii) SJLIFE diagnosed 1962-2012 (N = 2182). To evaluate the effect of cancer treatment on the background genetic predisposition to DM, we estimated standardized effect sizes (Z’) among EA survivors in each abdominal radiation group for 398 index variants from the largest population-based EA DM study. Radiation group Z’ estimates were compared using linear regression. Results: In the original CCSS cohort we identified nine variants associated with DM and provide further support for four linked variants in the ERCC6L2 locus. Among all survivors, the rs55849673-A allele was associated with increased odds for DM among survivors in the original CCSS cohort (minor allele frequency [MAF]-cases = 0.055; MAF-controls = 0.024; adjusted odds ratio [aOR] = 2.9, 95% CI: 2.0-4.2, P = 3.7×10-8). Allele frequencies were consistent in the CCSS expansion (MAF-cases = 0.075; MAF-controls = 0.028; P = 0.07) and SJLIFE (MAF-cases = 0.036; MAF-controls = 0.027; P = 0.5). Additionally, rs55849673-A estimates were consistent among EA survivors and stronger among survivors not treated with abdominal radiation (MAF-cases = 0.052; MAF-controls = 0.021; aOR = 3.6, P = 1.6×10-6). Notably, in the CCSS expansion all rs55849673-A EA carriers who developed DM did not receive abdominal radiation (MAF-cases = 0.1; MAF-controls = 0.026; P = 0.04). More broadly, the Z’ of population-based DM index variants were 78% lower in survivors treated with abdominal radiation than survivors not treated with abdominal radiation (beta = 0.22; P = 0.01), indicating the background genetic risk for DM may be altered by treatment. Conclusions: We provide evidence for a novel locus of DM in childhood cancer survivors. This locus is a regulatory region associated with expression of ERCC6L2, a gene implicated in an East Asian population-based DM study. Taken together, our findings support the overwhelming effect of abdominal radiation on DM risk in childhood cancer survivors, relative to other risk factors, and provide insight on a genetic locus that may be useful for DM risk prediction in the context of cancer treatment.

Incidence and Economic Burden of Infections in Cancer Patients Receiving Immune Checkpoint Inhibitors: A Retrospective Cohort Study

2020 ◽  
Author(s):  
Swarna Nalluru ◽  
Paramrajan Piranavan ◽  
Anvesh Narimiti ◽  
Ahmad D. Siddiqui ◽  
George M. Abraham
Keyword(s):  
Risk Factors ◽  
Cancer Patients ◽  
Economic Burden ◽  
Immune Checkpoint ◽  
Average Cost ◽  
Immune Checkpoint Inhibitors ◽  
Multidisciplinary Approach ◽  
Checkpoint Inhibitors ◽  
Antitumor Effects ◽  
Cost Per Admission

Abstract BACKGROUNDAlong with antitumor effects, Immune Checkpoint Inhibitors (ICPI) have shown great potential in treating chronic infections such as HIV, Hepatitis B and malaria, in ex-vivo studies. However, several case reports and case series have suggested an increased infection risk in cancer patients. The purpose of our study was to assess the risk of infections in cancer patients receiving ICPI. We also attempted to evaluate the role of a multidisciplinary approach (Oncology and Infectious disease specialists) and the cost associated with treatment. METHODS:Records on all cancer patients over age ≥18 years old who had received at least one dose of ICPI between 2015 to 2018 at a major community teaching hospital in the central Massachusetts region were reviewed. Several risk factors associated with infection were identified. A two-tailed, unpaired t-test was used to analyze the association between risk factors and infection. We calculated the cumulative length of stay (LOS) and cost per admission with a multidisciplinary vs. non-multidisciplinary approach. The calculated total average cost per admission was compared to a matched population (without an oncologic diagnosis) admitted with infections similar to that in our study, to compare the economic burden. RESULTSRetrospective chart review of 169 cancer patients receiving ICPI showed sixty-two episodes of infection in thirty-seven (21.8%) patients and a mortality rate of 3.5% due to associated complications. Risk factors like COPD, prior chemotherapy and steroid use were significantly associated (P<0.05) with infections. Further sub-group analysis showed increase in cumulative LOS from 5.9 to 8.1 days but approximately similar average cost per admission ($52,047 vs. $54,510) with non-multidisciplinary vs. multidisciplinary approach. The calculated total cost per admission during an episode of infection in this cohort of patients was $35,484; three-fold higher when matched to similar infections in a general non-oncologic population ($11,527). CONCLUSIONSA significant incidence of infections and associated health care resource utilization continues to prevail in cancer patients despite the utility of ICPI. A multidisciplinary approach to manage the infections and associated complications in cancer patients receiving ICPI increased the cumulative LOS but not the average cost per admission.

scholarly journals Prognostic Factors and Biomarkers of Responses to Immune Checkpoint Inhibitors in Lung Cancer

2019 ◽  
Vol 20 (19) ◽  
pp. 4931 ◽  
Author(s):  
Andrea Bianco ◽  
Fabio Perrotta ◽  
Giusi Barra ◽  
Umberto Malapelle ◽  
Danilo Rocco ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cell ◽  
Cancer Treatment ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
T Cell Subsets ◽  
Durable Response ◽  
Lung Cancer Treatment ◽  
The Impact

Manipulation of the immune response is a game changer in lung cancer treatment, revolutionizing management. PD1 and CTLA4 are dynamically expressed on different T cell subsets that can either disrupt or sustain tumor growth. Monoclonal antibodies (MoAbs) against PD1/PDL1 and CTLA4 have shown that inhibitory signals can be impaired, blocking T cell activation and function. MoAbs, used as both single-agents or in combination with standard therapy for the treatment of advanced non-small cell lung cancer (NSCLC), have exhibited advantages in terms of overall survival and response rate; nivolumab, pembrolizumab, atezolizumab and more recently, durvalumab, have already been approved for lung cancer treatment and more compounds are in the pipeline. A better understanding of signaling elicited by these antibodies on T cell subsets, as well as identification of biological determinants of sensitivity, resistance and correlates of efficacy, will help to define the mechanisms of antitumor responses. In addition, the relevance of T regulatory cells (Treg) involved in immune responses in cancer is attracting increasing interest. A major challenge for future research is to understand why a durable response to immune checkpoint inhibitors (ICIs) occurs only in subsets of patients and the mechanisms of resistance after an initial response. This review will explore current understanding and future direction of research on ICI treatment in lung cancer and the impact of tumor immune microenvironment n influencing clinical responses.

scholarly journals Do checkpoint inhibitors compromise the cancer patients’ immunity and increase the vulnerability to COVID-19 infection?

Immunotherapy ◽  
2020 ◽  
Author(s):  
Joseph Kattan ◽  
Clarisse Kattan ◽  
Tarek Assi
Keyword(s):  
Cancer Therapy ◽  
Severe Acute Respiratory Syndrome ◽  
Cancer Patients ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Survival Outcomes ◽  
Toxicity Profile ◽  
Anti Cancer ◽  
Acquired Immunodeficiency ◽  
Improvement In Survival

The severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) has been declared a pandemic by the WHO that claimed the lives of thousands of people within a few months. Cancer patients represent a vulnerable population due to the acquired immunodeficiency associated with anti-cancer therapy. Immune checkpoint inhibitors have largely impacted the prognosis of a multitude of malignancies with significant improvement in survival outcomes and a different, tolerable toxicity profile. In this paper, we assess the safety of ICI administration in cancer patients during the coronavirus pandemic in order to guide the usage of these highly efficacious agents.

scholarly journals Adverse Effects of Immune-Checkpoint Inhibitors in Hepatocellular Carcinoma

2020 ◽  
Vol Volume 13 ◽  
pp. 11725-11740
Author(s):  
Tian-ming Cui ◽  
Yao Liu ◽  
Jia-bei Wang ◽  
Lian-xin Liu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Adverse Effects ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors
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