Repeat Peptide Receptor Radionuclide Therapy in Neuroendocrine Tumors: A NET Center of Excellence Experience.

INTRODUCTION: The available data for the safety and efficacy of repeat peptide receptor radionuclide therapy (PRRT) are almost exclusively from European centers. We present an updated experience with repeat PRRT in a cohort of US patients with neuroendocrine tumors (NETs) at our NET center of excellence. METHODS: We used our single-center longitudinal NET registry to identify patients who had been previously treated with at least one dose of PRRT (PRRT 1, either 177Lu DOTATATE or 90Y DOTATOC) and following radiographic disease progression were re-treated with a second course of PRRT (PRRT 2). We reviewed patient, tumor and treatment characteristics, objective response rates, and toxicities after PRRT 1 and PRRT 2. RESULTS: A total of 11 patients were included in the analysis. 45.5% (5/11) of patients received 177Lu DOTATATE PRRT only, both for PRRT1 and PRRT 2, while 54.5% (6/11) of patients received 90Y DOTATOC PRRT for PRRT1. At first restaging scan after PRRT2 (3-6 months), 18.2% (2/11), 36.4% (4/11), and 27.3% (3/11) of patients had PR, SD, and PD, respectively; 2/11 patients (18.2%) died before the first restaging scan. Therefore, 5/11 (45.5%) patients were noted to have disease progression. Median PFS for PRRT1 was 25.4 months and median PFS for PRRT2 was 13.1 months (p = 0.0001). We did not find a statistically significant difference between the occurrence of short and long-term hematological toxicities as well as renal toxicity after PRRT1 and PRRT2. CONCLUSION: We show that repeat PRRT may benefit select patients and have an acceptable safety profile. In our cohort, PFS was significantly lower after PRRT2 as compared to PRRT1.

Novel chimeric antigen receptor targets and constructs for acute lymphoblastic leukemia: Moving beyond CD19.

Acute lymphoblastic leukemia (ALL) is the second most common acute leukemia in adults with a poor prognosis with relapsed or refractory (R/R) B-cell lineage ALL (B-ALL). Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has shown excellent response rates in RR B-ALL, but most patients relapse due to poor persistence of CAR T-cell therapy or other tumor-associated escape mechanisms. In addition, anti-CD19 CAR T-cell therapy causes several serious side effects such as cytokine release syndrome and neurotoxicity. In this review, we will discuss novel CAR targets, CAR constructs, and various strategies to boost CARs for the treatment of RR B-ALL. In addition, we discuss a few novel strategies developed to reduce the side effects of CAR.

Sickle cell disease and coronavirus disease-2019 (COVID-19) infection: a single-center experience.

PURPOSE: Sickle cell disease (SCD) has been found to be associated with an increased risk of hospitalization and death from coronavirus disease-2019 (COVID-19). We sought to study clinical outcomes in patients with SCD and a diagnosis of COVID-19 infection. METHODS: We conducted a retrospective analysis of adult patients (>18 years) with SCD who were diagnosed with COVID-19 infection between 1 March 2020 and 31 March 2021. Data on baseline characteristics and overall outcomes were collected and analyzed using SAS 9.4 for Windows. RESULTS: A total of 51 patients with SCD were diagnosed with COVID-19 infection in the study period, out of which 39.3% were diagnosed and managed in the outpatient setting/emergency room (ER) and 60.3% in the inpatient setting. Disease-modifying therapy such as hydroxyurea did not impact inpatient vs outpatient/ER management (P > 0.05). Only 5.71% (n = 2) required intensive care unit admission and were mechanically ventilated and 3.9% (2 patients) died of complications of COVID-19 infection. CONCLUSION: We identified a lower mortality (3.9%) rate among patients in our cohort in comparison to previous studies and a higher burden of inpatient hospitalizations as compared to outpatient/ER management. Further prospective data are needed to validate these findings. Key messages What is already known on this topic COVID-19 has been shown to have a disproportionately unfavorable impact on African Americans, including longer hospital stays, higher rates of ventilator dependence, and a higher overall mortality rate. Limited data also suggest that sickle cell disease (SCD) is associated with an increased risk of hospitalization and death from COVID-19. What this study adds Our analysis did not show a higher mortality due to COVID-19 in patients with SCD. However, we identified a high burden of inpatient hospitalizations in this population. COVID-19-related outcomes did not improve with the use of disease-modifying therapies. How this study might affect research, practice, or policy These results will aid in decision making for triage of patients with COVID-19 and SCD and ensure the most appropriate use of healthcare resources. Our analysis underscores the need for more robust data to identify patients at higher risk of severe disease and/or mortality, necessitating inpatient hospitalization and aggressive management.

Safety of catheter ablation for atrial fibrillation in patients with cancer: a nationwide cohort study.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia in patients with cancer, especially breast, gastrointestinal, respiratory, urinary tract, and hematological malignancies. Catheter ablation (CA) is a well-established, safe treatment option in healthy patients; however, literature regarding safety of CA for AF in patients with cancer is limited and confined to single centers. OBJECTIVE: We aimed to assess the outcomes and peri-procedural safety of CA for AF in patients with certain types of cancer. METHODS: The NIS database was queried between 2016 and 2019 to identify primary hospitalizations with AF and CA. Hospitalizations with secondary diagnosis of atrial flutter and other arrhythmias were excluded. Propensity score matching was used to balance the covariates between cancer and non-cancer groups. Logistic regression was used to analyze the association. RESULTS: During this period, 47,765 CA procedures were identified, out of which 750 (1.6%) hospitalizations had a diagnosis of cancer. After propensity matching, hospitalizations with cancer diagnosis had higher in-hospital mortality (OR 3.0, 95% CI 1.5-6.2, p = 0.001), lower home discharge rates (OR 0.7, 95% CI 0.6-0.9, p < 0.001) as well as other complications such as major bleeding (OR 1.8, 95% CI 1.3-2.7, p = 0.001) and pulmonary embolism (OR 6.1, 95% CI 2.1-17.8, p < 0.001) but not associated with any major cardiac complications (OR 1.2, 95% CI 0.7-1.8, p = 0.53). CONCLUSION: Patients with cancer who underwent CA for AF had significantly higher odds of in-hospital mortality, major bleeding, and pulmonary embolism. Further larger prospective observational studies are needed to validate these findings.

Using Shared Medical Appointments for Delivering Patient-Centered Care to Cancer Survivors: A Feist-Weiller Cancer Center Pilot Study.

Background: Shared medical appointments (SMAs) have shown promise in the care of patients with conditions such as diabetes; however, the impact of lifestyle medicine-based SMAs on the overall health status of cancer survivors remains poorly understood. Materials and Methods: This cross-sectional survey of patients was conducted to study the impact of a unique lifestyle medicine-based survivorship program on cancer survivors. Results: A total of 64 patients were telephonically contacted for the survey, out of which 39 (60.9%) patients responded. All patients (39 of 39, 100%) found the program to be helpful in some way; 26 patients (66.7%) found SMAs to be significantly helpful, while 13 patients (33.3%) found SMAs as only somewhat helpful. The majority noted feeling a great sense of support (35 of 39, 89.7%), followed by improvement in appetite (21 of 39, 54%) and improvement in pain (14 of 39, 35.9%). All patients reported at least some improvement in subjective well-being (SWB); patients who attended >3 appointments reported significant/very significant improvement in SWB (P = .03). Conclusion: SMAs offer promise in the effective delivery of lifestyle medicine-focused care to cancer survivors. Further prospective studies are needed to validate these findings.

Financial Burden of Drugs Prescribed for Cancer-Associated Symptoms.

PURPOSE: The financial toxicity of anticancer drugs is well-documented, but little is known about the costs of drugs used to manage cancer-associated symptoms. METHODS: We reviewed relevant guidelines and compiled drugs used to manage seven cancer-associated symptoms (anorexia and cachexia, chemotherapy-induced peripheral neuropathy, constipation, diarrhea, exocrine pancreatic insufficiency, cancer-associated fatigue, and chemotherapy-induced nausea and vomiting). Using GoodRx website, we identified the retail price (cash price at retail pharmacies) and lowest price (discounted, best-case scenario of out-of-pocket costs) for patients without insurance for each drug or formulation for a typical fill. We describe lowest prices here. RESULTS: For anorexia and cachexia, costs ranged from $5 US dollars (USD; generic olanzapine or mirtazapine tablets) to $1,156 USD (brand-name dronabinol solution) and varied widely by formulation of the same drug or dosage: for olanzapine 5 mg, $5 USD (generic tablet) to $239 USD (brand-name orally disintegrating tablet). For chemotherapy-induced peripheral neuropathy, costs of duloxetine varied from $12 USD (generic) to $529 USD (brand-name). For constipation, the cost of sennosides or polyethylene glycol was <$15 USD, whereas newer agents such as methylnaltrexone were expensive ($1,001 USD). For diarrhea, the cost of generic loperamide or diphenoxylate-atropine tablets was <$15 USD. For exocrine pancreatic insufficiency, only brand-name formulations were available, range of cost, $1,072 USD-$1,514 USD. For cancer-associated fatigue, the cost of generic dexamethasone or dexmethylphenidate was <$15 USD, whereas brand-name modafinil was more costly ($1,284 USD). For a 4-drug nausea and vomiting prophylaxis regimen, costs ranged from $181 USD to $1,430 USD. CONCLUSION: We highlight the high costs of many symptom control drugs and the wide variation in the costs of these drugs. These findings can guide patient-clinician discussions about cost-effectively managing symptoms, while promoting the use of less expensive formulations when possible.

Analysis of the impact of COVID-19 pandemic on house-staff in the USA: addressing the ripple effects.

Background: The novel corona virus has changed the way individuals interact with each other and society. In the medical sector, this has affected the residents and fellows who spend the majority of their time on the front lines. Methods: We conducted a cross-sectional survey to assess the impact of the COVID-19 pandemic on the lives and training of house-staff across the USA. Respondents in our survey reported feeling significantly overwhelmed by the ongoing pandemic. Results: The majority of house-staff were significantly concerned about the lack of protective equipment, inability to safeguard themselves from infection and inability to look after their families. Concerns regarding contracting the infection and transmitting it to their loved ones were reported as a cause of mental distress among resident physicians. Increasing patient load, lack of protective equipment, and disruption of educational and academic activities during the COVID-19 pandemic have all reportedly affected the training and overall well-being of resident physicians. Conslusion: Our study adds further support for measures to safeguard house-staff with proper protective equipment and ensure adequate support for both mental and physical well-being during these challenging times.

Possible mechanisms responsible for acute coronary events in COVID-19.

The novel coronavirus (SARS-CoV-2) is primarily a respiratory pathogen and its clinical manifestations are dominated by respiratory symptoms, the most severe of which is acute respiratory distress syndrome (ARDS). However, COVID-19 is increasingly recognized to cause an overwhelming inflammatory response and cytokine storm leading to end organ damage. End organ damage to heart is one of the most severe complications of COVID-19 that increases the risk of death. We proposed a two-fold mechanism responsible for causing acute coronary events in patients with COVID-19 infection: Cytokine storm leading to rapid onset formation of new coronary plaques along with destabilization of pre-existing plaques and direct myocardial injury secondary to acute systemic viral infection. A well-coordinated immune response is the first line innate immunity against a viral infection. However, an uncoordinated response and hypersecretion of cytokines and chemokines lead to immune related damage to the human body. Human Coronavirus (HCoV) infection causes infiltration of inflammatory cells that cause excessive production of cytokines, proteases, coagulation factors, oxygen radicals and vasoactive molecules causing endothelial damage, disruption of fibrous cap and initiation of formation of thrombus. Systemic viral infections also cause vasoconstriction leading to narrowing of vascular lumen and stimulation of platelet activation via shear stress. The resultant cytokine storm causes secretion of hypercoagulable tissue factor without consequential increase in counter-regulatory pathways such as AT-III, activated protein C and plasminogen activator type 1. Lastly, influx of CD4+ T-cells in cardiac vasculature results in an increased production of cytokines that stimulate smooth muscle cells to migrate into the intima and generate collagen and other fibrous products leading to advancement of fatty streaks to advanced atherosclerotic lesions. Direct myocardial damage and cytokine storm leading to destabilization of pre-existing plaques and accelerated formation of new plaques are the two instigating mechanisms for acute coronary syndromes in COVID-19.

Role of Mitochondrial Markers in Improved Detection and Risk-Stratification in Barrett's Esophagus Patients.

Barrett's esophagus (BE) is the only known precursor of esophageal adenocarcinoma (EAC) and is amenable to treatment. However, more than 90 percent of EAC patients are never diagnosed with antecedent BE. Identification of molecular markers for BE is needed to improve detection of BE through efficient non-endoscopic methods that are cost-effective, sensitive and can be used to cater to a larger group of the population at risk. Alterations in mitochondria and mitochondrial DNA have been shown to be associated with various cancers, including esophageal cancer. Mitochondrial response to oxidative stress, alterations in mitochondrial metabolism, changes in mitochondrial membrane potential and mitochondrial genetic mutations have been found to be associated with BE pathogenesis. This mini-review focuses on the role of mitochondria in the pathogenesis of BE and EAC and the prospects of using that knowledge to develop effective strategies for the improved detection and risk-stratification in BE patients.