The Value Proposition of Observation Medicine in Managing Acute Oncologic Pain.

PURPOSE OF REVIEW: Despite recommended best practice guidelines, pain remains an ongoing but undertreated symptom in patients with cancer, many of whom require emergency department evaluation for acute oncologic pain. A significant proportion of these patients are hospitalized for pain management, which increases healthcare costs and exposes patients to the risks of hospitalization. We reviewed the literature on observation medicine: an emerging mode of healthcare delivery which can offer patients with acute pain access to a hospital's pain management solutions and specialists without an inpatient hospitalization. Specifically, we appraised the role of observation medicine in acute pain management and its financial implications in order to consider its potential impact on the management of acute oncologic pain. RECENT FINDINGS: Recent evidence shows that observation medicine has the potential to decrease short-stay hospitalizations in cancer patients presenting with various concerns, including pain. Observation medicine is reported to be successful in providing comprehensive and cost-effective care for non-cancer patients with acute pain, making it a promising alternative to short-stay hospitalizations for cancer patients with acute oncologic pain.

Bupropion XL and SR have similar effectiveness and adverse event profiles when used to treat smoking among patients at a comprehensive cancer center.

BACKGROUND AND OBJECTIVES: Bupropion extended-release (XL; once-daily dosing) has equal efficacy with the sustained-release (SR) formulation (twice-daily dosing) for treating depression, but no studies have compared the two formulations for the treatment of smoking. In a naturalistic open-label study, we compared the effectiveness and the adverse event profiles of XL and SR in treating cancer patients for smoking. METHODS: Cancer patients (N = 648) were prescribed bupropion XL (n = 454) or SR (n = 194) alone or in combination with nicotine replacement therapy (NRT) for treating smoking from September 2006 to December 2017. We analyzed 7-day point prevalence abstinence at end-of-treatment (EOT; 3 months postmedication initiation) and evaluated for noninferiority. We also analyzed the adverse event profile differences between the medications. RESULTS: There were no significant differences in abstinent rates at EOT between bupropion XL and SR when using intent-to-treat models, regardless of concomitant NRT. XL demonstrated noninferiority in treatment efficacy compared to SR when excluding those on combined treatment with NRT. Further, there were no significant differences in spontaneously reported adverse events between XL and SR. CONCLUSIONS: Our data did not reveal a difference between bupropion XL and SR formulations in terms of effectiveness or adverse event profiles among cancer patients prescribed bupropion alone or in combination with NRTs to quit smoking. SCIENTIFIC SIGNIFICANCE: In this first published direct comparison of their effectiveness and adverse event profiles, we found that bupropion XL is likely therapeutically equivalent to bupropion SR when treating smoking among cancer patients, and produces similar side effects.

A modified emergency severity index level is associated with outcomes in cancer patients with COVID-19.

OBJECTIVE: To evaluate a modified emergency severity index (mESI)-based triage of cancer patients with coronavirus disease 2019 (COVID-19) in the emergency department (ED) and determine the associations between mESI level and ED disposition, hospital length of stay, and overall survival. METHODS: Medical records were retrospectively reviewed for all patients who presented to our institution's ED between March 22, 2020, and March 12, 2021, and tested positive for SARS-CoV-2. RESULTS: A total of 306 cancer patients tested positive for SARS-CoV-2, with 45% of patients triaged to level 2 (emergent) and 55% to level 3 (urgent). Among all patients, 61.8% were admitted to the hospital, 15.7% were admitted to the intensive care unit, 2.9% were sent for observation, and 19.6% were discharged. Although demographic and clinical characteristics did not significantly vary by triage level, we observed significant differences in ED length of stay (urgent = 6.67 h, emergent = 5.97 h; p < 0.01). Hospital and intensive care unit admission rates were also significantly higher among emergent patients than among urgent patients (p < 0.05). There were 75 deaths (urgent = 32; emergent = 43), and the 30-day mortality rate was significantly higher among emergent patients (urgent = 8%, emergent = 15%; p < 0.05). The mESI level persisted as a significant factor associated with overall survival (hazard ratio = 1.7, 95% confidence interval = 1.09-2.81) in multivariable analysis. CONCLUSION: The mESI level is associated with ED disposition, ED length of stay, and overall survival in cancer patients presenting with COVID-19. These results indicate that the mESI triage tool can be effectively used in cancer patients with COVID-19, whose condition can rapidly deteriorate.

"Triple Threat" Conditions Predict Mortality Among Patients With Advanced Cancer Who Present to the Emergency Department.

BACKGROUND: Delirium, poor performance status, and dyspnea predict short survival in the palliative care setting. OBJECTIVE: Our goal was to determine whether these three conditions, which we refer to as a "triple threat," also predict mortality among patients with advanced cancers in the emergency department (ED). METHODS: The study sample included 243 randomly selected, clinically stable patients with advanced cancer who presented to our ED. The analysis included patients who had delirium (Memorial Delirium Assessment Scale score ≥ 7), poor performance status (Eastern Cooperative Oncology Group performance status score of 3 or 4), or dyspnea as a presenting symptom. We obtained survival data from medical records. We calculated predicted probability of dying within 30 days and association with number of symptoms after the ED visit using logistic regression analysis. RESULTS: Twenty-eight patients died within 30 days after presenting to the ED. Death within 30 days occurred in 36% (16 of 44) of patients with delirium, 28% (17 of 61) of patients with poor performance status, and 14% (7 of 50) of patients with dyspnea, with a predicted probability of 30-day mortality of 0.38 (95% confidence interval [CI] 0.25-0.53), 0.28 (95% CI 0.18-0.40), and 0.15 (95% CI 0.07-0.29), respectively. The predicted probability of death within 30 days for patients with two or three of the conditions was 0.49 (95% CI 0.34-0.66) vs. 0.05 (95% CI 0.02-0.09) for patients with none or one of the conditions. CONCLUSIONS: Patients with advanced cancers who present to the ED and have at least two triple threat conditions have a high probability of death within 30 days.

Impact of Checkpoint Inhibitor Immunotherapy, Primarily Pembrolizumab, on Infection Risk in Patients With Advanced Lung Cancer: A Comparative Retrospective Cohort Study.

BACKGROUND: Checkpoint inhibitor (CPI) immunotherapy has revolutionized cancer treatment. However, immune-related adverse events and the risk of infections are not well studied. To assess the infectious risk of CPIs, we evaluated the incidence of infections in lung cancer patients treated with CPIs plus conventional chemotherapy (CC) vs CC alone. METHODS: We performed a retrospective comparative study of patients with advanced non-small cell lung cancer who received CPIs combined with CC and those treated with CC alone at our institution during January 2016 to February 2019. We compared clinical characteristics, treatments, and outcomes including infection rate and mortality between the groups. RESULTS: We identified 123 patients for the CPI group and 147 patients for the control (CC) group. Eighteen patients (15%) in the CPI group and 33 patients (22%) in the control group developed infections (P = .1). Pneumonia was the most common infection encountered in both groups. Urinary tract infection was higher in the CC group (40%) than in the CPI group (9%) (P = .01). On multivariable analysis, chronic obstructive pulmonary disease (P = .024), prior use of corticosteroids (P = .021), and neutropenia (P < .001) were independent risk factors for infection and severe infection requiring hospital admission. Chronic kidney disease (P = .02), prior cancer treatment (P = .023), and neutropenia (P < .0001) were identified as independent risk factors for all-cause mortality. CONCLUSIONS: Lung cancer patients treated with CPIs combined with CC have a comparable risk of infection to those treated with CC alone, although there is a trend towards fewer infections in those given CPIs, particularly when it comes to urinary tract infections.

Cardiotoxicity associated with immune checkpoint inhibitors and CAR T-cell therapy.

INTRODUCTION: The expanding use of immunotherapy and the growing population of patients with cancer has led to an increase in the reporting of immune related adverse events (irAEs). The emergency clinician should be aware of these emerging toxicities, some of which can be fatal. In this review we discuss the cardiotoxic side effects of immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T-cell (CAR T-cell) therapy. DISCUSSION: Recognizing the possible presentations of cardiotoxic irAEs is of utmost important as the diagnosis of cardiotoxicity associated with ICI and CAR T-cell can be difficult to make in the emergency department. The emergency clinician will have to presume the diagnosis and treat it without final confirmation in most cases. For this reason, if the diagnosis is suspected, early involvement of the cardiologist and oncologist is important to help guide management. Most irAEs will be treated with glucocorticoids, but in the case of CAR T-cell cardiotoxicity, Tocilizumab should be used as first line. CONCLUSION: Although cardiotoxicity is rare, it is often life-threatening. Treatment should be initiated as soon as the diagnosis is suspected, and early involvement of the cardiologist and oncologist is imperative for optimal treatment.

Clinical and Cancer-Related Predictors for Venous Thromboembolism in Cancer Patients Presenting to the Emergency Department.

BACKGROUND: The accurate detection of cancer-associated venous thromboembolism (VTE) can avoid unnecessary diagnostic imaging or laboratory tests. OBJECTIVE: We sought to determine clinical and cancer-related risk factors of VTE that can be used as predictors for oncology patients presenting to the emergency department (ED) with suspected VTE. METHODS: We retrospectively analyzed all consecutive patients who presented with suspicion of VTE to The University of Texas MD Anderson Cancer Center ED between January 1, 2009, and January 1, 2013. Logistic regression models were used to identify risk factors that were associated with VTE. The ability of these factors to predict VTE was externally validated using a second cohort of patients who presented to King Hussein Cancer Center ED between January 1, 2009, and January 1, 2016. RESULTS: Cancer-related covariates associated with the occurrence of VTE were high-risk cancer type (odds ratio [OR] 3.64 [95% confidence interval {CI} 2.37-5.60], p < 0.001), presentation within 6 months of the cancer diagnosis (OR 1.92 [95% CI 1.62-2.28], p < 0.001), active cancer (OR 1.35 [95% CI 1.10-1.65], p = 0.003), advanced stage (OR 1.40 [95% CI 1.01-1.94], p = 0.044), and the presence of brain metastasis (OR 1.73 [95% CI 1.32-2.27], p < 0.001). When combined, these factors along with other clinical factors showed high prediction performance for VTE in the external validation cohort. CONCLUSIONS: Cancer risk group, presentation within 6 months of cancer diagnosis, active and advanced cancer, and the presence of brain metastases along with other related clinical factors can be used to predict VTE in patients with cancer presenting to the ED.

Adverse Effects of Immune Checkpoint Therapy in Cancer Patients Visiting the Emergency Department of a Comprehensive Cancer Center.

STUDY OBJECTIVE: Cancer immunotherapy is evolving rapidly and is transforming cancer care. During the last decade, immune checkpoint therapies have been developed to enhance the immune response; however, specific adverse effects related to autoimmunity are increasingly apparent. This study aims to fill the knowledge gap related to the spectrum of immune-related adverse effects among cancer patients visiting emergency departments (EDs). METHODS: We performed a retrospective review of patients treated with immune checkpoint therapy who visited the ED of a comprehensive cancer center between March 1, 2011, and February 29, 2016. Immune-related adverse effects from the ED visits were identified and profiled. We analyzed the association of each immune-related adverse effect with overall survival from the ED visit to death. RESULTS: We identified 1,026 visits for 628 unique patients; of these, 257 visits (25.0%) were related to one or more immune-related adverse effects. Diarrhea was the most common one leading to an ED visit. The proportions of ED visits associated with diarrhea, hypophysitis, thyroiditis, pancreatitis, or hepatitis varied significantly by immune checkpoint therapy agent. Colitis was significantly associated with better prognosis, whereas pneumonitis was significantly associated with worse survival. CONCLUSION: Cancer patients treated with ipilimumab, nivolumab, or pembrolizumab may have a spectrum of immune-related adverse effects that require emergency care. Future studies will need to update this profile as further novel immunotherapeutic agents are added.

Association of emergency department admission and early inpatient palliative care consultation with hospital mortality in a comprehensive cancer center.

PURPOSE: Consultation to palliative care (PC) services in hospitalized patients is frequently late after admission to a hospital. The purpose of this study is to examine the association of in-hospital mortality and timing of palliative care consultation in cancer patients admitted through the emergency department (ED) of MD Anderson Cancer Center. METHODS: Institutional databases were queried for unique medical admissions over a period of 1 year. Primary cancer type, ED versus direct admission, length of stay (LOS), presenting symptoms, and in-hospital mortality were reviewed; patient data were analyzed, and risk factors for in-hospital mortality were identified. The association of early palliative care consultation (within 3 days of admission) with these outcomes was studied. Descriptive statistics and multivariate logistic regression model were used. RESULTS: Equal numbers of patients were admitted directly versus through the ED (7598 and 7538 respectively). However, of all patients who died in the hospital, 990 (88%) were admitted through the ED, compared with 137 admitted directly (P < 0.001). Patients who died in the hospital had longer median LOS compared with patients who were discharged alive (11 vs. 4 days, respectively, P < 0.001). Early palliative care consultation was associated with decreased mortality, compared with late consultation (P < 0.001). Chief complaints of respiratory problems, neurologic issues, or fatigue/weakness were significantly associated with in-hospital mortality. CONCLUSION: We found an association between ED admission and hospital mortality. Decedent cancer patients had a prolonged LOS, and early palliative care consultation for terminally ill symptomatic patients may prevent in-hospital mortality and improve quality of cancer care.

Diabetic ketoacidosis induced by a single dose of pembrolizumab.

Immune checkpoint inhibitors are a new class of anticancer drugs recently approved by the US Food and Drug Administration (FDA) for the treatment of various malignancies. Pembrolizumab is an immune checkpoint inhibitor that targets the programmed cell death protein-1 (PD-1) receptor and blocks its interaction with programmed cell death ligand-1 (PD-L1) and programmed cell death ligand-2 (PD-L2). Pembrolizumab was first approved by the FDA in 2014 for the treatment of advanced melanoma and is currently approved for use in non-small cell lung cancer and several other neoplasms. Immune checkpoint inhibitors such as pembrolizumab have been reported to induce immune-mediated side effects, including type 1 diabetes mellitus in very rare cases (0.1% in clinical trials). Here, we report the case of a woman with no known history of diabetes who presented to our emergency department in a state of diabetic ketoacidosis within 3 weeks of receiving only a single dose of pembrolizumab therapy, and without any previous exposure to immunotherapy. This case of abrupt adult-onset type 1 diabetes mellitus is an example of the undesirable side effects that can emerge after only a brief exposure to an immune checkpoint inhibitor. Close monitoring of patients receiving immune checkpoint inhibitors is warranted for the early diagnosis and management of imminent and potentially life-threatening complications.

Biomarkers of Sepsis and Bloodstream Infections: The Role of Procalcitonin and Proadrenomedullin With Emphasis in Patients With Cancer.

Sepsis and bloodstream infections remain a leading cause of death in immunocompromised patients with cancer. The management of these serious infections consist of empiric use of antimicrobial agents which are often overused. Procalcitonin and proadrenomedullin are biomarkers that have been extensively evaluated in the general populations but with little emphasis in the population immunocompromised patients with cancer, where they may have promising roles in the management of febrile patients. In this review, we summarize the available evidence of the potential role of these available biomarkers in guiding antimicrobial therapy to optimize the use of resources in the general patient population. Special emphasis is given to the role of these 2 biomarkers in the immunocompromised and critically ill patients with cancer, highlighting the distinctive utility of each.

Improvement of Smoking Abstinence Rates With Increased Varenicline Dosage: A Propensity Score-Matched Analysis.

PURPOSE/BACKGROUND: It is unclear whether increasing the dose of varenicline beyond the standard dose of 2 mg/d would improve smoking abstinence. METHODS: We examined the effect of 3 mg/d of varenicline on smoking abstinence among smokers who had reduced their smoking by 50% or more in response to 2 mg/d for at least 6 weeks but had not quit smoking. Of 2833 patients treated with varenicline, dosage of a subset of 73 smokers was increased to 3 mg/d after 6 weeks. We used a propensity score analysis involving multiple baseline covariates to create a comparative sample of 356 smokers who remained on 2 mg/d. All smokers received concurrent and similar smoking-cessation counseling. RESULTS: At 3 months, we found higher 7-day point prevalence smoking-abstinence rate in the 3-mg group (26%) than in the 2-mg group (11.5%, χ = 10.60, P < 0.001; risk ratio [RR], 2.3; 95% confidence interval [CI], 1.4-3.6). The difference in abstinence rates remained significant at the 6-month (P < 0.001; RR, 2.6; 95% CI, 1.6-3.9) and 9-month follow-up (P < 0.001; RR, 2.2; 95% CI, 1.4-3.3). CONCLUSIONS: A relatively small increase in the daily dose of varenicline seems to offer a benefit for those who are not able to achieve total abstinence after approximately 6 weeks of 2 mg/d.

Advance care planning: challenges at the emergency department of a cancer care center.

INTRODUCTION: Code status discussions form an important part of advance care planning (ACP) as it enables physicians to respect the patient's wishes for end-of-life care. However, in some cases, code status discussions can be challenging causing the physician to go against the patient's wishes and the code of medical ethics. This is especially true in an emergency setting. In this paper, we will discuss three cases of advanced cancer patients, where code status discussions posed challenges to healthcare providers. CASE REPORTS: In the first case, the patient was a 26-year-old male diagnosed with advanced osteosarcoma. Code status was discussed with him, while he was still functional, wherein he agreed to a do-not-resuscitate (DNR) order. However, at the time of end-of-life care, despite of previous code status agreement, the patient's mother insisted on full code. As a result, the DNR order was reverted and the patient was intubated. The second case discusses an 83-year-old female patient with metastatic gastric cancer. Code status was extensively discussed with the patient and her son who agreed to sign a DNR order. This case posed a challenge because when the patient's condition deteriorated, her son demanded cardioversion and other aggressive treatment measures without any chest compressions or intubation. In the third case, the patient was a 40-year-old woman with advanced metastatic adenocarcinoma with neuroendocrine features of the parotid. On admission to the ED, as per the patient's wishes expressed by her husband, a DNR/DNI order was placed. However, this order had to be reverted when the patient's aunt and sister opposed vehemently to the DNR/DNI order. CONCLUSION: The three cases demonstrate the challenges that can arise in the implementation of code status order in the ED as it pertains for end-of-life care. In any scenario, respecting the patient's wishes and adherence to the code of medical ethics take precedence over any familial objections arising difficulties with coping.

Comparing Molnupiravir to Nirmatrelvir/Ritonavir (Paxlovid) in the Treatment of Mild-to-Moderate COVID-19 in Immunocompromised Cancer Patients.

BACKGROUND: Nirmatrelvir/Ritonavir has been shown to reduce the risk of COVID-19 progression by 88% compared to placebo, while Molnupiravir reduced it by 31%. However, these two agents have not been compared head-to-head. We therefore compared the safety and efficacy of both agents for the treatment of mild-to-moderate COVID-19 in immunocompromised cancer patients. METHODS: We identified 240 cancer patients diagnosed with COVID-19 and treated with Molnupiravir or Nirmatrelvir/Ritonavir. Patients were matched using a 1:2 ratio based on age group (18-64 years vs. ≥65) and type of cancer. The collected data included demographics, comorbidities, and treatment outcome. RESULTS: Both groups had comparable characteristics and presenting symptoms. However, dyspnea was more prevalent in the Molnupiravir group, while sore throat was more prevalent in the Nirmatrelvir/Ritonavir group. The rate of disease progression was comparable in both groups by univariate and multivariable analysis. Treatment with Molnupiravir versus Nirmatrelvir/Ritonavir revealed no significant difference in disease progression by multivariable analysis (adjusted OR = 1.31, 95% CI: 0.56-3.14, p = 0.70). Patients who received Nirmatrelvir/Ritonavir, however, were significantly more prone to having drug-drug interactions/adverse events (30% vs. 0%, p < 0.0001). CONCLUSIONS: In the treatment of mild-to-moderate COVID-19 in cancer patients, Molnupiravir was comparable to Nirmatrelvir/Ritonavir in preventing progression to severe disease/death and rebound events, and it had a superior safety profile.

Hemoptysis in Cancer Patients.

Hemoptysis in cancer patients can occur for various reasons, including infections, tumors, blood vessel abnormalities and inflammatory conditions. The degree of hemoptysis is commonly classified according to the quantity of blood expelled. However, volume-based definitions may not accurately reflect the clinical impact of bleeding. This review explores a more comprehensive approach to evaluating hemoptysis by considering its risk factors, epidemiology and clinical consequences. In particular, this review provides insight into the risk factors, identifies mortality rates associated with hemoptysis in cancer patients and highlights the need for developing a mortality prediction score specific for cancer patients. The use of hemoptysis-related variables may help stratify patients into risk categories; optimize the control of bleeding with critical care; implement the use of tracheobronchial or vascular interventions; and aid in treatment planning. Effective management of hemoptysis in cancer patients must address the underlying cause while also providing supportive care to improve patients' quality of life.

Emergency department use by patients who received chimeric antigen receptor T cell infusion therapy.

Background: Chimeric antigen receptor T cell infusion (CAR T) therapy has revolutionized the treatment of hematologic malignancies, but treatment-related toxicities are of concern. Understanding the timing and reasons for which patients present to the emergency department (ED) after CAR T therapy can assist with the early recognition and management of toxicities. Methods: A retrospective observational cohort study was conducted for patients who had undergone CAR T therapy in the past 6 months and visited the ED of The University of Texas MD Anderson Cancer Center between 04/01/2018 and 08/01/2022. The timing of presentation after CAR T product infusion, patient characteristics, and outcomes of the ED visit were examined. Survival analyses were conducted using Cox proportional hazards regression and Kaplan-Meier estimates. Results: During the period studied, there were 276 ED visits by 168 unique patients. Most patients had diffuse large B-cell lymphoma (103/168; 61.3%), multiple myeloma (21/168; 12.5%), or mantle cell lymphoma (16/168; 9.5%). Almost all 276 visits required urgent (60.5%) or emergent (37.7%) care, and 73.5% of visits led to admission to the hospital or observation unit. Fever was the most frequent presenting complaint, reported in 19.6% of the visits. The 30-day and 90-day mortality rates after the index ED visits were 17.0% and 32.2%, respectively. Patients who had their first ED visit >14 days after CAR T product infusion had significantly worse overall survival (multivariable hazard ratio 3.27; 95% confidence interval 1.29-8.27; P=0.012) than patients who first visited the ED within 14 days of CAR T product infusion. Conclusion: Cancer patients who receive CAR T therapy commonly visit the ED, and most are admitted and/or require urgent or emergent care. During early ED visits patients mainly present with constitutional symptoms such as fever and fatigue, and these early visits are associated with better overall survival.

Long COVID in cancer patients: preponderance of symptoms in majority of patients over long time period.

Background: An increasing number of observational studies have reported the persistence of symptoms following recovery from acute COVID-19 disease in non-cancer patients. The long-term consequences of COVID-19 are not fully understood particularly in the cancer patient population. The purpose of this study is to assess post-acute sequelae of SARS-CoV-2 infection (PASC) in cancer patients following acute COVID-19 recovery. Methods: We identified cancer patients at MD Anderson Cancer Center who were diagnosed with COVID-19 disease between March 1, 2020, and September 1, 2020, and followed them till May 2021. To assess PASC, we collected patients reported outcomes through questionnaires that were sent to patients daily for 14 days after COVID-19 diagnosis then weekly for 3 months, and then monthly thereafter. We also reviewed patients' electronic medical records to capture the persistence or emergence of new COVID19-related symptoms reported during any clinic or hospital encounter beyond 30 days of the acute illness and up to 14 months. Results: We included 312 cancer patients with a median age of 57 years (18-86). The majority of patients had solid tumors (75%). Of the 312 patients, 188 (60%) reported long COVID-19 symptoms with a median duration of 7 months and up to 14 months after COVID-19 diagnosis. The most common symptoms reported included fatigue (82%), sleep disturbances (78%), myalgias (67%), and gastrointestinal symptoms (61%), followed by headache, altered smell or taste, dyspnea (47%), and cough (46%). A higher number of females reported a persistence of symptoms compared to males (63% vs. 37%; p=0.036). Cancer type, neutropenia, lymphocytopenia, and hospital admission during acute COVID-19 disease were comparable in both groups. Among the 188 patients with PASC, only 16 (8.5%) were re-admitted for COVID-related reasons. Conclusions: More than one out of two cancer patients, and more likely females, report PASC that may persist beyond 6 months and even 1 year. The most common symptoms are non-respiratory and consist of fatigue, sleep disturbance, myalgia, and gastrointestinal symptoms. Most of the cancer patients with PASC were managed on outpatient basis with only 8.5% requiring a COVID-19-related re-admission. Funding: This research is supported by the National Institutes of Health/National Cancer Institute under award number P30CA016672, which supports the MD Anderson Cancer Center Clinical Trials Office. The funders had no role in study design, data collection, and interpretation, or the decision to submit the work for publication.

International multicenter study comparing COVID-19 in patients with cancer to patients without cancer: Impact of risk factors and treatment modalities on survivorship.

Background: In this international multicenter study, we aimed to determine the independent risk factors associated with increased 30 day mortality and the impact of cancer and novel treatment modalities in a large group of patients with and without cancer with COVID-19 from multiple countries. Methods: We retrospectively collected de-identified data on a cohort of patients with and without cancer diagnosed with COVID-19 between January and November 2020 from 16 international centers. Results: We analyzed 3966 COVID-19 confirmed patients, 1115 with cancer and 2851 without cancer patients. Patients with cancer were more likely to be pancytopenic and have a smoking history, pulmonary disorders, hypertension, diabetes mellitus, and corticosteroid use in the preceding 2 wk (p≤0.01). In addition, they were more likely to present with higher inflammatory biomarkers (D-dimer, ferritin, and procalcitonin) but were less likely to present with clinical symptoms (p≤0.01). By country-adjusted multivariable logistic regression analyses, cancer was not found to be an independent risk factor for 30 day mortality (p=0.18), whereas lymphopenia was independently associated with increased mortality in all patients and in patients with cancer. Older age (≥65y) was the strongest predictor of 30 day mortality in all patients (OR = 4.47, p<0.0001). Remdesivir was the only therapeutic agent independently associated with decreased 30 day mortality (OR = 0.64, p=0.036). Among patients on low-flow oxygen at admission, patients who received remdesivir had a lower 30 day mortality rate than those who did not (5.9 vs 17.6%; p=0.03). Conclusions: Increased 30 day all-cause mortality from COVID-19 was not independently associated with cancer but was independently associated with lymphopenia often observed in hematolgic malignancy. Remdesivir, particularly in patients with cancer receiving low-flow oxygen, can reduce 30 day all-cause mortality. Funding: National Cancer Institute and National Institutes of Health.

The Emerging Role of the Gut Microbiome in the Cancer Response to Immune Checkpoint Inhibitors: A Narrative Review.

The discovery of immune checkpoint inhibitors (ICIs) has revolutionized the care of cancer patients. However, the response to ICI therapy exhibits substantial interindividual variability. Efforts have been directed to identify biomarkers that predict the clinical response to ICIs. In recent years, the gut microbiome has emerged as a critical player that influences the efficacy of immunotherapy. An increasing number of studies have suggested that the baseline composition of a patient's gut microbiota and its dysbiosis are correlated with the outcome of cancer immunotherapy. This review tackles the rapidly growing body of evidence evaluating the relationship between the gut microbiome and the response to ICI therapy. Additionally, this review highlights the impact of antibiotic-induced dysbiosis on ICI efficacy and discusses the possible therapeutic interventions to optimize the gut microbiota composition to augment immunotherapy efficacy.