The impact of cancer metastases on COVID-19 outcomes: A COVID-19 and Cancer Consortium registry-based retrospective cohort study.

BACKGROUND: COVID-19 can have a particularly detrimental effect on patients with cancer, but no studies to date have examined if the presence, or site, of metastatic cancer is related to COVID-19 outcomes. METHODS: Using the COVID-19 and Cancer Consortium (CCC19) registry, the authors identified 10,065 patients with COVID-19 and cancer (2325 with and 7740 without metastasis at the time of COVID-19 diagnosis). The primary ordinal outcome was COVID-19 severity: not hospitalized, hospitalized but did not receive supplemental O2, hospitalized and received supplemental O2, admitted to an intensive care unit, received mechanical ventilation, or died from any cause. The authors used ordinal logistic regression models to compare COVID-19 severity by presence and specific site of metastatic cancer. They used logistic regression models to assess 30-day all-cause mortality. RESULTS: Compared to patients without metastasis, patients with metastases have increased hospitalization rates (59% vs. 49%) and higher 30 day mortality (18% vs. 9%). Patients with metastasis to bone, lung, liver, lymph nodes, and brain have significantly higher COVID-19 severity (adjusted odds ratios [ORs], 1.38, 1.59, 1.38, 1.00, and 2.21) compared to patients without metastases at those sites. Patients with metastasis to the lung have significantly higher odds of 30-day mortality (adjusted OR, 1.53; 95% confidence interval, 1.17-2.00) when adjusting for COVID-19 severity. CONCLUSIONS: Patients with metastatic cancer, especially with metastasis to the brain, are more likely to have severe outcomes after COVID-19 whereas patients with metastasis to the lung, compared to patients with cancer metastasis to other sites, have the highest 30-day mortality after COVID-19.

Impact of COVID-19 in patients on active melanoma therapy and with history of melanoma.

INTRODUCTION: COVID-19 particularly impacted patients with co-morbid conditions, including cancer. Patients with melanoma have not been specifically studied in large numbers. Here, we sought to identify factors that associated with COVID-19 severity among patients with melanoma, particularly assessing outcomes of patients on active targeted or immune therapy. METHODS: Using the COVID-19 and Cancer Consortium (CCC19) registry, we identified 307 patients with melanoma diagnosed with COVID-19. We used multivariable models to assess demographic, cancer-related, and treatment-related factors associated with COVID-19 severity on a 6-level ordinal severity scale. We assessed whether treatment was associated with increased cardiac or pulmonary dysfunction among hospitalized patients and assessed mortality among patients with a history of melanoma compared with other cancer survivors. RESULTS: Of 307 patients, 52 received immunotherapy (17%), and 32 targeted therapy (10%) in the previous 3 months. Using multivariable analyses, these treatments were not associated with COVID-19 severity (immunotherapy OR 0.51, 95% CI 0.19 - 1.39; targeted therapy OR 1.89, 95% CI 0.64 - 5.55). Among hospitalized patients, no signals of increased cardiac or pulmonary organ dysfunction, as measured by troponin, brain natriuretic peptide, and oxygenation were noted. Patients with a history of melanoma had similar 90-day mortality compared with other cancer survivors (OR 1.21, 95% CI 0.62 - 2.35). CONCLUSIONS: Melanoma therapies did not appear to be associated with increased severity of COVID-19 or worsening organ dysfunction. Patients with history of melanoma had similar 90-day survival following COVID-19 compared with other cancer survivors.

Characteristics of clinical trials for haematological malignancies from 2015 to 2020: A systematic review.

BACKGROUND: As the landscape of haematological malignancies dramatically changes due to diagnostic and therapeutic advances, it is important to evaluate trends in clinical trial designs. The objective of our study was to describe the design of clinical trials for five common haematological malignancies with respect to randomisation and end-points. We also aimed to assess trends over time and examine the relationships of funding source and country of origin to proportions of randomisation and utilisation of clinical end-points. METHODS: This systematic review identified haematological malignancy clinical trials starting in 2015-2020 registered at ClinicalTrials.gov as of 20th February 2021. Trial-related variables including randomisation status, type of primary end-point, and both projected and actual enrolment numbers were captured. Clinical end-points were defined as overall survival and quality of life, while surrogate end-points included all other end-points. RESULTS: Of 2609 relevant trials included in this analysis, only one-fifth were randomised (538, 21%), with a significant decrease in the proportion of randomised clinical trials from 26% of trials in 2015 to 19% in 2020 (p < 0.00001). Between the years 2015 and 2020, the proportion of randomised trials for all haematological malignancies using primary surrogate end-points remained relatively consistent, ranging from 84% in 2015 to 78% in 2020 (p = 0.352). Overall, only 15% of trials utilised primary end-points of overall survival or quality of life in a randomised design. CONCLUSIONS: This systematic review of haematological malignancy trials found that the majority of trials are non-randomised and that there has been an increase in the ratio of non-randomised to randomised studies over time. The vast majority of randomised haematological malignancy trials use surrogate primary end-points.

Hospitalization at the end of life in patients with multiple myeloma.

BACKGROUND: Despite advances in treatment, multiple myeloma (MM) remains incurable and results in significant morbidity and mortality. Further research investigating where MM patients die and characterization of end-of-life hospitalizations is needed. METHODS: We utilized the National Inpatient Sample (NIS) to explore the hospitalization burden of MM patients at the end of their lives. RESULTS: The percent of patients dying in the hospital as a percent of overall MM deaths ranged from 54% in 2002 to 41.4% in 2017 (p < 0.01). Blood transfusions were received in 32.7% of these hospitalizations and infections were present in 47.8% of patients. Palliative care and/or hospice consultations ranged from 5.3% in 2002 to 31.4% in 2017 (p < 0.01). CONCLUSION: Our study demonstrates that patients with MM dying in the hospital have a significant requirement for blood transfusions and have a high infection burden. We also show that palliative care and hospice involvement at the end of life has increased over time but remains low, and that ultimately, inpatient mortality has decreased over time, but MM patients die in the hospital at a higher rate than the general population.

Total Neoadjuvant Therapy vs Standard Therapy in Locally Advanced Rectal Cancer: A Systematic Review and Meta-analysis.

Importance: Standard therapy for locally advanced rectal cancer includes concurrent chemoradiotherapy followed by surgery and adjuvant chemotherapy (CRT plus A). An alternative strategy known as total neoadjuvant therapy (TNT) involves administration of CRT plus neoadjuvant chemotherapy before surgery with the goal of delivering uninterrupted systemic therapy to eradicate micrometastases. A comparison of these 2 approaches has not been systematically reviewed previously. Objective: To determine the differences in rates of pathologic complete response (PCR), disease-free and overall survival, sphincter-preserving surgery, and ileostomy between patients receiving TNT vs standard CRT plus A. Data Sources: MEDLINE (via PubMed) and Embase (via OVID) were searched from inception through July 1, 2020, for the following terms: anal/anorectal neoplasms OR anal/anorectal cancer AND total neoadjuvant treatment OR total neoadjuvant therapy. Only studies in English were included. Study Selection: Randomized clinical trials or prospective/retrospective cohort studies comparing outcomes in patients with locally advanced rectal cancer who received TNT vs CRT plus A. Data Extraction and Synthesis: Data regarding the first author, publication year, location, sample size, and rates of PCR, sphincter-preserving surgery, ileostomy, and disease-free and overall survival were extracted using Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and pooled using a random-effects model. Main Outcomes and Measures: Rates of PCR, sphincter-preserving surgery, ileostomy, and disease-free and overall survival. Results: After reviewing 2165 reports, 7 unique studies including a total of 2416 unique patients, of whom 1206 received TNT, were selected. The median age for the patients receiving TNT ranged from 57 to 69 years, with 58% to 73% being male. The pooled prevalence of PCR was 29.9% (range, 17.2%-38.5%) in the TNT group and 14.9% (range, 4.2%-21.3%) in the CRT plus A group. Total neoadjuvant therapy was associated with a higher chance of achieving a PCR (odds ratio [OR], 2.44; 95% CI, 1.99-2.98). No statistically significant difference in the proportion of sphincter-preserving surgery (OR, 1.06; 95% CI, 0.73-1.54) or ileostomy (OR, 1.05; 95% CI, 0.76-1.46) between recipients of TNT and CRT plus A was observed. Only 3 studies presented data on disease-free survival, and pooled analysis showed significantly higher odds of improved disease-free survival in patients who received TNT (OR, 2.07; 95% CI, 1.20-3.56; I2 = 49%). Data on overall survival were not consistently reported. Conclusions and Relevance: The findings of this systematic review and meta-analysis suggest that TNT is a promising strategy in locally advanced rectal cancer, with superior rates of PCR compared with standard therapy. However, the long-term effect on disease recurrence and overall survival needs to be explored in future studies.

Immune Checkpoint Inhibitors versus VEGF Targeted Therapy as Second Line Regimen in Advanced Hepatocellular Carcinoma (HCC): A Retrospective Study.

Several targeted agents including multi-tyrosine kinase inhibitors (mTKIs) and immunotherapy (IO) agents have been approved for use beyond the frontline setting in patients with advanced hepatocellular carcinoma (HCC). Due to lack of prospective head-to-head comparative trials, there is no standardized way for alternating those agents beyond frontline. Therefore, we performed a retrospective review of the Kansas University (KU) cancer registry to determine whether IO may be superior to non-IO therapy. Patients with advanced HCC were divided into two groups based on the second-line systemic regimen received (IO vs. non-IO). Progression-free survival (PFS) and overall survival (OS) were calculated under the Kaplan-Meier and Cox proportional hazards models. No statistically significant differences in PFS and OS were found, although a non-significant delayed separation in the survival curve favoring IO was identified (median PFS 3.9 months vs. 3 months; median OS 10 months vs. 10 months respectively for IO vs. non-IO). This retrospective analysis is one of the earliest and largest studies comparing second-line IO and non-IO therapies thus far reported. Future studies should aim to define specific biomarkers for response prediction and treatment optimization based on individual patient and tumor characteristics. Furthermore, combinatorial therapeutic strategies is an evolving approach showing early promising signal.

Inpatient mortality of patients with multiple myeloma and renal impairment undergoing autologous stem cell transplantation.

OBJECTIVES: Further data are needed on the safety of high-dose melphalan and autologous stem cell transplant (HDM-ASCT) in patients with multiple myeloma (MM) and renal impairment. The objective of our study was to use the National Inpatient Sample (NIS) to determine inpatient mortality for patients with MM and renal impairment undergoing HDM-ASCT, as well as trends over time. METHODS: Using the NIS, we tracked hospital admissions for MM patients from 2002 to 2014 who underwent HDM-ASCT, using ICD 9 coding. RESULTS: The total weighted estimate of inpatient admissions for HDM-ASCT among MM patients was 47,253 from 2002 to 2014. A weighted total of 45 and 1709 patients with MM received peritoneal dialysis (PD) and hemodialysis (HD) during HDM-ASCT for MM, respectively. There was a markedly increased risk of inpatient mortality in patients on dialysis undergoing transplant (20.5% for PD patients, 13.8% for HD patients), even after accounting for other comorbidities (odds ratio of inpatient mortality of 6.193 [CI 3.585-10.701]). A significant decrease was noted in inpatient mortality for patients with ESRD undergoing HDM-ASCT over time from 15.6% in 2009 to 5% in 2014 (P < .001). CONCLUSION: Patients with MM on dialysis undergoing HDM-ASCT are at significantly increased risk of inpatient mortality.

Trends and Outcomes of Gastrointestinal Bleeding Among Septic Shock Patients of the United States: A 10-Year Analysis of a Nationwide Inpatient Sample.

Introduction Gastrointestinal bleeding (GIB) complicating septic shock (SS) presents a therapeutic challenge in intensive care units. Large-scale data regarding utilization, length of stay, and cost outcomes of this association are lacking. Methods We queried the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample from 2003 to 2012, and identified all adult patients aged ≥18 years hospitalized for SS by the International Classification of Diseases, Ninth Revision (ICD-9) diagnostic code for SS and GIB. We compared the baseline characteristics and outcomes among patients with SS plus GIB to patients with SS without GIB. Results The weighted sample size from 2003 to 2012 was 119,684 admissions for SS. Among them, 6,571 (5.4%) patients were found to have a GIB. The mean age of the SS population with and without GIB was (mean/standard error of mean) [70.85 (0.43) vs. 67.43 (0.13) P < 0.001, respectively]. The incidence of GIB over the course of 10 years has remained stable; however, the mortality associated with GIB among SS patients is found to be declining especially from 2008 (59.2%) to 2012 (45.1%) (P < 0.01). Patients with SS and GIB compared to patients with SS and no GIB were found to have a longer length of stay [20.56 (0.61) vs. 15.76 (0.13) P < 0.001], higher mortality [54% vs. 45% P < 0.001], and higher admission costs in United States dollar ($) (mean/SEM) [$192,524.89 (7,378.20) vs. $142,688.55 (1,336.65) P < 0.001]. Univariate analysis demonstrated that comorbid conditions like peptic ulcer disease and cirrhosis had significant odds ratios {1.56 and 1.709, P = 0.016 and 0.046 respectively} for the occurrence of GIB with SS. Gastroesophageal reflux disease was found to be associated with a lower incidence of GIB [odds ratio: 0.57, P = 0.0008]. The cause of sepsis (pneumonia, urinary tract infection, or abdominal infections) was not a significant distinguishing factor for the incidence of GIB in SS. Conclusion GIB continues to affect the patients with SS admitted in intensive care units in the United States. We found an incidence of 5.4% of GIB in patients with SS, and it was associated with worse outcomes.

Gastrointestinal Bleeding in Patients With Acute Respiratory Distress Syndrome: A National Database Analysis.

BACKGROUND: The goal of our study was to determine the impact of gastrointestinal bleeding (GIB) on in-hospital outcomes among acute respiratory distress syndrome (ARDS) patients, and subsequently determine the potential risk factors for the development of GIB. METHODS: ARDS patients with and without GIB were identified using the National Inpatient Sample (2002 - 2012). Linear regression analysis was used to assess impact of GIB on in-hospital mortality, length of stay and total charges. Univariate logistic regression was used to determine associated odds ratios (OR) for causes of ARDS and common comorbid conditions. RESULTS: We identified 149,190 ARDS patients. The incidence of GIB was the highest among patients > 60 years (P < 0.001). GIB was associated with longer hospitalization days (7.3 days versus 11.9 days, P < 0.001), higher mortality (11% versus 27%, P < 0.001) and greater economic burden ($82,812 versus $45,951, P < 0.001). GIB was common in cirrhosis (OR: 8.3), peptic ulcer disease (OR: 3.7), coagulopathy disorders (OR: 3.003), thrombocytopenia (OR: 2.6), anemia (OR: 2.5) and atrial fibrillation (OR: 1.5). ARDS secondary to aspiration pneumonia (OR: 2.0), pancreatitis (OR: 2.0), sepsis (OR: 1.6) and community acquired pneumonia (OR: 0.8) was more likely to have GIB. CONCLUSION: Our study demonstrates that GIB in ARDS patients is associated with significant increased mortality, hospitalization and health care cost.

Relevance of B-Lines on Lung Ultrasound in Volume Overload and Pulmonary Congestion: Clinical Correlations and Outcomes in Patients on Hemodialysis.

BACKGROUND: Volume overload in patients on hemodialysis (HD) is an independent risk factor for cardiovascular mortality. B-lines detected on lung ultrasound (BLUS) assess extravascular lung water. This raises interest in its utility for assessing volume status and cardiovascular outcomes. METHODS: End-stage renal disease patients on HD at the Island Rehab Center being older than 18 years were screened. Patients achieving their dry weight (DW) had a lung ultrasound in a supine position. Scores were classified as mild (0-14), moderate (15-30), and severe (>30) for pulmonary congestion. Patients with more than 60 were further classified as very severe. Patients were followed for cardiac events and death. RESULTS: 81 patients were recruited. 58 were males, with a mean age of 59.7 years. 44 had New York Heart Association (NYHA) class 1, 24 had class 2, and 13 had class 3. In univariate analysis, NYHA class was associated with B-line classes (<0.001) and diastolic dysfunction (0.002). In multivariate analysis, NYHA grade strongly correlated with B-line classification (0.01) but not with heart function (0.95). 71 subjects were followed for a mean duration of 1.19 years. 9 patients died and 20 had an incident cardiac event. A Kaplan-Meier survival analysis demonstrated an interval decrease in survival times in all-cause mortality and cardiac events with increased BLUS scores (p = 0.0049). Multivariate Cox regression analysis showed the independent predictive value of BLUS class for mortality and cardiac events with a heart rate of 2.98 and 7.98 in severe and very severe classes, respectively, compared to patients in the mild class (p = 0.025 and 0.013). CONCLUSION: At DW, BLUS is an independent risk factor for death and cardiovascular events in patients on HD.

Leptomeningeal Carcinomatosis in Recurrent Non-Small Cell Lung Cancer: A Case Report and Review of Current Treatment Modalities.

Leptomeningeal carcinomatosis (LC) is an uncommon sequelae of non-small cell lung cancer. The treatment modalities for LC have historically been limited with an overall poor prognosis. This case report outlines a 76-year-old female who presented with recurrence of non-small cell lung cancer as LC. LC is difficult to treat, and options include radiation, chemotherapy (systemic and intrathecal), as well as targeted therapies. This case outlines a unique approach and reviews the current literature on the effectiveness of these options in non-small cell lung cancer.

The impact of specialized oncology nursing on patient supportive care outcomes.

Meeting the supportive care needs of cancer patients remains a challenge to cancer care systems around the world. Despite significant improvements in the organization of medical care of patients with cancer, numerous surveys of cancer populations demonstrate that significant proportions of patients fail to have their supportive care needs met. One possible solution is the introduction of a care coordinator role using oncology nursing to help ensure that patients' physical, psychological, and social support needs are addressed. Although having face validity, there is little empirical evidence on the effects of nurse-led supportive care coordinator roles on patient reported supportive care outcomes. In this article the authors present the results of a prospective longitudinal cohort study of 113 patients referred to a community-based specialist oncology nursing program. Using validated instruments they found significant improvements in patient-reported outcomes in key supportive care domains: unmet needs, quality of life, and continuity of care, as well as a shift in patterns of health resource utilization from acute care settings to the community over the course of the intervention. The results of this study are important in supporting the design and development of controlled trials to examine provider roles in the coordination of supportive cancer care.

Quantitative evaluation of single-arm versus randomized phase II cancer clinical trials.

BACKGROUND: There is a debate among cancer researchers about the use of single-arm or randomized phase II clinical trial designs; however, there is limited published objective evaluation of this issue. PURPOSE: To objectively quantify the impact on phase III clinical trials of a policy of all single-arm versus all randomized phase II trials. METHODS: A simulation study was performed comparing optimal single-arm and randomized phase II trial designs with a variety of commonly used α and ß error rates. Parameters modeled included: between-institution variability in the standard of care response rate, between-institution variability in the treatment effect, between-institution variability in the estimate of historical control rate (for selecting H0), presence of historical bias, and proportion of phase II trials conducted using active agents. RESULTS: Using single-arm phase II trials resulted in a higher percentage of phase III trials conducted using active agents when there was minimal standard of care activity, or in the presence of a positive historical bias (H0 estimated to be greater than truth). Randomized phase II trials performed better in the presence of a negative historical bias, in the presence of high variability, and were more consistent across variation of historical bias. The proportion of phase III trials conducted using active agents was increased by reducing the α error. Presence of historical bias and the proportion of active agents studied in phase II had the greatest influence on results. LIMITATIONS: It was estimated that between 5% and 20% of agents studied in phase II trials are active; however, the conclusions could change if this estimate is incorrect. This study did not account for the possibility of a new drug application submission immediately following phase II. The primary outcome looked at was response rate, although some investigators have suggested that time-to-event outcomes should be used in phase II, particularly for randomized phase II trials. CONCLUSIONS: Both single-arm and randomized phase II trials appear warranted in certain situations. Investigators should increase consideration of the potential impact on phase III trials to optimally select the proper trial design prior to phase II study implementation.