bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of cancer on emergency department outcomes.
Authors: Qian Alexander S. , Qiao Edmund M. , Nalawade Vinit , Voora Rohith S. , Kotha Nikhil V. , Dameff Christian , Coyne Christopher John , Murphy James Don
Published: June 2021

e18618

Background: Cancer patients frequently utilize the Emergency Department (ED) for a variety of diagnoses, both related and unrelated to their cancer. Patients with cancer have unique risks related to their cancer and treatment which could influence ED-related outcomes. A better understanding of these risks could help improve risk-stratification for these patients and help inform future interventions. This study sought to define the increased risks cancer patients face for inpatient admission and hospital mortality among cancer patients presenting to the ED. Methods: From the National Emergency Department Sample (NEDS) we identified patients with and without a diagnosis of cancer presenting to the ED between 2016 and 2018. We used International Classification of Diseases, version 10 (ICD10-CM) codes to identify patients with cancer, and to identify patient’s presenting diagnosis. Multivariable mixed-effects logistic regression models assessed the influence of cancer diagnoses on two endpoints: hospital admission from the ED, and inpatient hospital mortality. Results: There were 340 million weighted ED visits, of which 8.3 million (2.3%) occurred in patients with a cancer diagnosis. Compared to non-cancer patients, patients with cancer had an increased risk of inpatient admission (64.7% vs. 14.8%; p < 0.0001) and hospital mortality (4.6% vs. 0.5%; p < 0.0001). Factors associated with both an increased risk of hospitalization and death included older age, male gender, lower income level, discharge quarter, and receipt of care in a teaching hospital. We identified the top 15 most common presenting diagnoses among cancer patients, and among each of these diagnoses, cancer patients had increased risks of hospitalization (odds ratio [OR] range 2.0-13.2; all p < 0.05) and death (OR range 2.1-14.4; all p < 0.05) compared to non-cancer patients with the same diagnosis. Within the cancer patient cohort, cancer site was the most robust individual predictor associated with risk of hospitalization or death, with highest risk among patients with metastatic cancer, liver and lung cancers compared to the reference group of prostate cancer patients. Conclusions: Cancer patients presenting to the ED have high risks for hospital admission and death when compared to patients without cancer. Cancer patients represent a distinct population and may benefit from cancer-specific risk stratification or focused interventions tailored to improve outcomes in the ED setting.
Tazemetostat (TAZ) in relapsed/refractory (R/R) follicular lymphoma (FL): Propensity-score matched analysis of E7438-G000-101 trial outcomes.
Authors: Proudman David , Gupta Deepshekhar , Nellesen Dave , Wong Alex , Yang Jay , Kamp Beth , Mamlouk Khalid
Published: June 2021

e18627

Background: Oncology drug development often requires the use of non-randomized, open-label, phase 2 basket studies to better understand the early activity and safety of a potential new therapy. As such, baseline demographics and disease characteristics may differ between cohorts which can impact the perception of efficacy between cohorts. TAZ, a first-in-class, oral enhancer of zeste homolog 2 (EZH2) inhibitor was approved by the US FDA after demonstrating single-agent, antitumor activity in a phase 2 study in adults with wild-type (WT) or mutant (MT) EZH2 R/R FL who had received ≥2 prior systemic therapies (NCT01897571). Differences between the cohorts in baseline characteristics known to be prognostic for clinical outcomes were noted, with the WT EZH2 cohort enrolling more patients with poor-risk features. This analysis assessed outcomes in the 2 groups after minimizing differences in baseline characteristics by creating a matched sample of directly comparable WT and MT patients. Methods: Propensity scores for each WT (n = 54) and MT (n = 45) EZH2 patient in the study were generated, based on the likelihood of being selected given their baseline characteristics. Characteristics identified for inclusion in the model were chosen if they were prognostic based on peer-reviewed literature and where larger differences were observed between cohorts at baseline: ECOG performance status, number of prior lines of anticancer therapy, progression of disease within 24 months, double refractory status, and prior history of hematopoietic stem cell transplant. Patients were matched 1:1 on propensity score, using a nearest-neighbor approach with caliper restrictions. Baseline covariates between the two matched groups were found to be sufficiently balanced. Objective response rate (ORR) point estimates were measured for the matched WT and MT EZH2 groups, and progression-free survival (PFS) was described using Kaplan-Meier analyses. Results: The propensity-matched sample included 56 patients (28 WT and 28 MT). Prior to matching, ORR was 35% (95% CI [22%, 48%]) in the WT and 69% (95% CI [55%, 83%]) in MT EZH2 groups; after matching, the ORR was 50% (95% CI [31%, 69%]) and 71% (95% CI [54%, 88%]), respectively. Median PFS was 11.1 months (95% CI [5.4, 16.7]) in the WT and 13.8 months (95% CI [11.1, 22.1]) in the MT EZH2 groups prior to matching, and 14.3 months (95% CI [11.1, inf]) and 14.8 (95% CI [10.7, inf]) months in the WT and MT EZH2 matched groups, respectively. Conclusions: As expected, efficacy remained higher in the MT EZH2 group; however, after adjustment, the ORR and PFS improved in the WT EZH2 group. This hypothesis-generating analysis suggests that outcomes in patients with WT EZH2 R/R FL treated with TAZ may have been more similar to those in the MT EZH2 group in the phase 2 trial had the baseline disease characteristics been more equally matched.
Biomarker testing in non-small cell lung cancer (NSCLC): An assessment of current practices in precision oncology in the community setting—A trial of the ECOG-ACRIN cancer research group (EAQ161CD).
Authors: Trosman Julia Rachel , Sicks Jorean , Weldon Christine B. , Tsongalis Gregory J. , Rapkin Bruce , Weaver Kathryn E. , Cohen Gary Irvin , Lad Thomas E. , Dressler Emily Van Meter , Stanfield Bill , Hopkins Judith O. , Hancock Judy , Kehn Heather , Steen Preston D. , Wagner Lynne I. , Carlos Ruth
Published: June 2021

e18649

Background: Molecular biomarker testing is integral to NSCLC cancer care, but adoption and testing practices in the community are varied and often suboptimal. Testing practices, such as standard testing protocols and results turnaround time (TAT), impact timely treatment decisions. We examined adoption and testing practices for guideline recommended NSCLC biomarkers among National Cancer Institute Community Research Program (NCORP) sites. The study was conducted in collaboration with Wake Forest NCORP Research Base. Methods: An online survey was administered to onsite labs affiliated with NCORP sites April 2019 – June 2020. We assessed testing practices for 7 NCCN recommended biomarkers, including 3 with category 1 recommendation (EGFR, ALK, PD-L1) and 4 with category 2 recommendations (BRAF, ROS1, MET, RET). Guideline concordant result TAT was defined as return of EGFR and ALK results in ≤ 10 days (Lindeman 2018) (see Table for other outcomes). We used proportions, including two-sided Fischer exact tests, to compare outcomes by site characteristics (safety net, practice size). Results: The survey response rate was 69% (58/85). All responding labs offered testing for category 1 biomarkers (EGFR, ALK and PD-L1); only 10% conducted these tests in-house (Table). The majority of labs also tested for category 2 biomarkers (67%). TAT varied, with most labs returning results in ≤ 10 days for EGFR and ALK (69%, but only a minority meet this TAT for all biomarkers. Larger practice size (> 1400 new cancer cases a year) was associated with in-house testing of EGFR, ALK, PD-L1 (p=0.03) and having standard testing protocols (p<0.001). Safety net affiliation did not significantly impact practices. Conclusions: We found universal adoption of NCCN category 1 biomarkers among the labs affiliated with NCORP sites, with the majority meeting guideline concordant results TAT. There is opportunity for improvement in adoption of category 2 biomarkers and result TAT, for example, by using standard testing protocols. Reassuringly, no difference in testing practices was detected by safety net affiliation.[Table: see text]
Clinical treatment pathways utilization in an outpatient academic cancer center.
Authors: Chen Anna , Park Seojin , Csik Valerie Pracilio , Maio Vittorio , Walsh Karen , Binder Adam F
Published: June 2021

e18673

Background: Clinical treatment pathway (CTP) tools have been incorporated into oncology practices to help standardize treatment, reduce care variation in cancer patients, and move towards value-based care. CTP tools incorporate the latest guidelines and are developed through multidisciplinary committees. Treatment decisions are prioritized by efficacy, toxicity, and cost to improve quality and value. This is especially important in cancer care which is associated with high drug costs. However, use and implementation of CTP tools has been met with mixed reviews and published data from academic medical centers are limited. Methods: Outpatient treatment decisions for patients across different cancer types, including colorectal, gastroesophageal, and breast cancers from July 2018 to March 2020 at an urban NCI-designated cancer center were evaluated. Every treatment decision was evaluated in relation to physician utilization of CTP tools. Treatment decisions were categorized as choosing a CTP recommended option ( pathways dependent), not choosing a CTP recommended option ( pathways independent), or not using the CTP tool at all ( non-pathways). Descriptive statistics and significance testing were used to explore CTP utilization over time, physician years in practice, cancer type, and cancer stage. Multinomial and binary logistic regression models were used to evaluate associated factors with CTP utilization. Results: During the study period, 1,007 treatment decisions were identified. Of these, 76% were pathways dependent, 13% were pathways independent, and 11% were non-pathways. CTP utilization was statistically significant in association with cancer type, cancer stage, physician years in practice, and year of encounter. In multinomial logistic regression models, physicians with more years in practice were more likely to be pathways independent and non-pathways than pathways dependent. Physicians treating colorectal or gastroesophageal cancer were more likely to be pathways independent [OR 3.27; 95% CI: 1.98-5.42 and OR 2.25; 95% CI: 1.12-4.49, respectively] or non-pathways [OR 2.98; 95% CI: 1.65-5.37 and OR 3.21; 95% CI: 1.58-6.54, respectively] than pathways dependent compared to physicians treating breast cancer. Treatment decisions for patients with either stage 2 and stage 4 cancers were more likely to be pathways independent than stage 1 cancers [OR 4.13; 95% CI: 1.44-11.84 and OR 4.37; 95% CI: 1.27-15.04, respectively]. Conclusions: This study found that a large proportion of treatment decisions for patients across different cancer types were made utilizing CTP tools, but utilization varies according to cancer type, stage, and physician years in practice. Further research is needed to better understand the physician decision making process and implementation of CTP tools to drive improvement in design, education, and training.
Improving admission medication reconciliation at a tertiary cancer center.
Authors: Kheder Ed , Saji Lijo , Zalpour Ali , Swanson Samuel , Mandayam Sreedhar
Published: June 2021

e18686

Background: Accurate medication reconciliation (MedRec) is a pivotal step ensuring patient safety during transition of care, yet one of the most challenging aspects in healthcare quality and safety. Inaccurate MedRec leads to 40 % of medications errors, 20% of which results in harm. Our aim is to increase rate of accurate MedRec completion at MD Anderson Cancer Center (MDACC), within 24 hours of admission, from 85% to >95% through Best Possible Medication History (BPMH) Methods: During pre-intervention phase, we audited medication review and reconciliation of 50 randomly selected patients within 24 hours from admission to MDACC. Our intervention included: conducting several brain-storming sessions with nursing staff, providers, pharmacists; creating fish bone diagram and process maps; designing educational presentations for nursing staff on how to practice BPMH; educating providers on how to complete medication reconciliation within 24 hours of admissions; assigning nursing champions; and sending email reminders to provider on a daily basis. We audited another 50 patients post intervention. In our project, BPMH accuracy was measured by percentage of patients with zero discrepancies (incorrect dosage, frequency or route; extra medication; discontinued medication not removed from list). Significance was tested for BPMH completion, and MedRec completion using a Binomial Test, while significance for number of discrepancies and audit completion time was tested using a Two Sample t-Test. Results: We collected data on 50 patients pre and 50 post intervention. Our results indicate statistically significant improvement in MedRec rate (100%), reduction of number of discrepancies and audit completion time. Conclusions: Medication review and reconciliation are multi-phased processes. Nurses, Pharmacists and medical providers are the cornerstone of accurate and complete MedRec. Reminder emails to medical providers played a key role in MedRec rate improvement. Additional root cause analysis is needed to further address the medication review completion process in our institution.[Table: see text]
Using randomized trial data to estimate effects of complex treatment regimens in real-world patients.
Authors: Webster-Clark Michael , Sanoff Hanna Kelly , Lund Jennifer Leigh , Sturmer Til , Westreich Daniel , Keil Alexander P.
Published: June 2021

e18706

Background: Real-world patients often differ from trial participants in prognostic factors such as age, sex, and cancer substage. New methods combine covariate data from real-world patients (the “target population”) with outcome and covariate data from a trial to estimate treatment effects in the target population that take these differences into account. With some assumptions, these methods can also estimate outcomes under treatment regimens not studied in the trial such as “what if we only gave six cycles of chemotherapy?” or “what if patients all perfectly followed a protocol?” Methods: Data from the MOSAIC trial of 5-fluorouracil (5FU) vs oxaliplatin + 5FU (FOLFOX) were combined with covariate data from a target population of stage III colon cancer patients in the US Oncology Network meeting trial eligibility criteria. We used weighting and G-computation to estimate five-year mortality and treatment-related paresthesia risk in the target population for four regimens: treatment with up to 12 cycles of 5FU, if providers used their discretion on dose reductions and delays (5FU-MD); up to 12 cycles of FOLFOX with similar physician discretion (FOLFOX-MD); up to 6 cycles of FOLFOX, with providers perfectly following a strict and specific protocol of dose reductions and delays (6-cycle FOLFOX-P, “P” for “per protocol”); and up to 12 cycles of FOLFOX, following the same strict protocol (12-cycle FOLFOX-P). Results: Tablepresents five-year all-cause mortality and paresthesia risk under each regimen in the stage III target population estimated from the models built in trial participants. Paresthesia risk increased with cumulative oxaliplatin dose. Estimated 5-year mortality was lowest with 12-cycle FOLFOX-P. Conclusions: In a target population of US Oncology Network patients with stage III colon cancer, strict protocols of 12 cycles of FOLFOX were predicted to improve survival compared to strict 6-cycle FOLFOX regimens or less strict 12-cycle FOLFOX and 5FU regimens at the cost of substantial increases in side effects. While estimates of risk differences in 5-year mortality were imprecise, combining trial and real-world data and then using weights and G-computation allowed estimation of benefits and harms of multiple regimens in a clinically relevant patient population.[Table: see text]
Assessment of differences in demographic characteristics and clinical diagnoses among black and white oncology patients with COVID.
Authors: Bhandari Sudip , Mueller Judith , Whyte Warren , Heilbroner Samuel P.
Published: June 2021

e18711

Background: Health disparities between black and white COVID-positive patients are well documented. To help address these disparities, clinicians need to understand the specific health challenges faced by black COVID patients compared to their white counterparts. These challenges are understudied in the oncologic setting. Hence, we present the demographic and clinical features of black COVID-positive cancer patients compared to whites. Methods: We used ConcertAI’s database of oncology EMR data, which includes clinical data from CancerLinQ Discovery. We conducted two-sample t-tests and chi-squared tests to measure the differences in black and white COVID-positive cancer patients across age, gender, ethnicity, state, region, ECOG, BMI, all cancer indications, stage, and Charlson comorbidities. COVID positivity was defined using claims data. Only relevant significant results are reported to save space. Results: Table summarizes the differences in 429 black and 980 white cancer patients with COVID. Black patients were younger, more likely to have an elevated BMI, and have a higher prevalence of breast cancer, congestive heart failure, diabetes, multiple myeloma, peptic ulcer disease, and renal disease. They also had less melanoma. Results were statistically significant at 0.05 level. Analyzing only black patients by COVID status shows very similar results. Conclusions: Black cancer patients suffer from multiple comorbid conditions that increase their risk of adverse outcomes when infected with COVID-19. The CDC lists eight comorbidities that put patients at a higher risk of severe COVID infection. Black patients in our cohort have a higher prevalence of four out of eight of these conditions—elevated BMI, renal disease, congestive heart failure, and diabetes. Clinicians should inspect for these comorbidities while treating this at-risk population. [Table: see text]
Chemotherapy at the end of life in colorectal and pancreatic cancer: Real-world data and trends over time.
Authors: Dunn Catherine , Lee Belinda , Shapiro Jeremy David , Wong Rachel , Gard Grace , Michael Michael , Hong Wei , Burge Matthew E. , Wong Vanessa , Thomson Ben , Ananda Sumitra , McLachlan Sue-Anne , Knowles Brett , Nikfarjam Mehdrad , Tie Jeanne , Jennens Ross , McKendrick Joseph James , Lee Margaret , Kosmider Suzanne , Gibbs Peter
Published: June 2021

e18723

Background: Chemotherapy at the end of life (CEOL) is widely accepted as an indicator of aggressive care. However, the evidence is limited primarily to single-centre experiences, with no consensus regarding acceptable benchmarks for CEOL, nor how this may be changing over time and with novel treatment options. We describe ‘real world’ CEOL in two large, multisite Australian registries of metastatic colorectal cancer (mCRC) and both locally advanced and metastatic pancreatic cancer (PC). Methods: Data was analysed from the TRACC and PURPLE registries, two large prospective multisite Australian cancer registries collecting prospective demographic, tumour, treatment and outcome data for mCRC and PC respectively. We identified all decedents between May 2009 and November 2020, determined the proportion who died within 14 or 30 days of chemotherapy (14D / 30D), or within 30D after a new line of therapy, defined as the first cycle of a new treatment regimen. Using univariate analysis, we compared baseline demographic and clinicopathological variables and trends over time. Results: 1505 mCRC and 602 PC decedents were identified. 20.9% of decedents (21.6% mCRC and 19.3% PC) received chemotherapy within 30D, and 11.5% within 14D (12.3% mCRC and 9.6% PC). There were lower rates of 30D CEOL after the first cycle of a new line of therapy (4.3% mCRC and 5.7% PC). Rates of CEOL decreased over the study period for mCRC (median rate of initial 3-year period 28% versus 15% in last 3-year period), but remained largely static for PC (18.9% versus 17.9%). 30D CEOL was more likely with palliative than curative intent treatment (mCRC OR 1.6, 95% CI 1.14-2.25, p = 0.007, PC OR 5.3, 95% CI 1.6-17.8), and advanced rather than local disease in PC (PC OR 2.59, 95%CI 1.6-4.1, p < 0.001). There was a trend towards CEOL and poorer performance status (ECOG) across all groups, only significant for 30D CEOL mCRC (OR 1.51, 95% CI 1.04-2.2). There was no association between CEOL and patient age, gender, Charlson comorbidity score or lines of therapy. Conclusions: Real-world rates of CEOL are higher in our cohorts of mCRC and PC patients than historical benchmarks but comparable to contemporary reports, which may be due to a wider array of available active treatments. Overall rates are decreasing over time for mCRC but static for PC, which may reflect the poorer overall survival for PC and lack of new effective therapies. The lower rates of death after new lines of therapy may signify that CEOL is more likely with existing treatment regimens and that clinicians are less likely to initiate a new chemotherapeutic regimen at EOL.
Association of proton pump inhibitors with survival in Veterans with non-small cell lung cancer receiving immunotherapy.
Authors: Stokes William A. , Behera Madhusmita , Jiang Renjian , Gutman David , Giuste Felipe , Burns Abigail , Sebastian Nikhil , Ramalingam Selvi , Sukhatme Vidula , Lowe Michael C. , Ramalingam Suresh S. , Sukhatme Vikas , Moghanaki Drew
Published: June 2021

e18729

Background: Proton pump inhibitors (PPI) can disrupt the gut microbiome and thereby modulate response to immunotherapy in cancer patients. In a recently published post-hoc analysis of 757 non-small cell lung cancer (NSCLC) patients receiving atezolizumab pooled from two prospective trials, overall survival (OS) and progression-free survival were significantly lower among the 234 patients receiving PPI. We investigated the impact of PPI in a larger cohort of NSCLC patients treated with ICI within the Veterans Health Administration. Methods: We conducted a nested cohort study of Veterans who were diagnosed with NSCLC between 2010 & 2018 and treated with ICI (immune checkpoint inhibitors). Exposure was defined as receipt of a PPI prescription within 90 days of an ICI infusion. Chi-square tests were used to compare characteristics of exposed versus unexposed Veterans. OS was measured from start of ICI. Cox proportional hazard multivariate (MV) regression was used to calculate hazard ratios (HR) corresponding to variables associated with OS. Results: We identified 3,634 Veterans receiving ICI with non-exclusive exposures to nivolumab (59.3%), pembrolizumab (35.1%), durvalumab (6.9%), and atezolizumab (3.3%). Their median age was 69, and a plurality had male gender (97.0%), white race (73.0%), comorbidity count ≥1 (60.4%), adenocarcinoma (47.8%), and stage IV disease at diagnosis (40.9%). In this nested cohort, 2,159 (59.4%) were exposed to PPI, predominantly omeprazole (1,264 or 85.6% of PPI group). Patients receiving PPI were more likely to be ≤71 years of age, to be white, to reside in rural areas, to have a higher comorbidity burden, to have adenocarcinoma histology, and to receive chemotherapy (all p≤0.04). On MV analysis, PPI use was not significantly associated with detriment in OS (HR 0.96 [0.89-1.04], p= 0.35). In the matched cohort analysis, median survival did not significantly differ between the 1,389 patients taking PPI and the 1,389 without PPI (median 10 versus 10 months, HR 0.98 [0.90-1.06], p= 0.59). Conclusions: In the largest analysis to date of concurrent PPI use in patients with NSCLC receiving ICI, there were no survival differences associated with concomitant PPI use. These results suggest that PPIs do not compromise ICI efficacy.
Comparison of population characteristics, treatment modes, and clinical outcomes of patients with advanced non-small cell lung cancer in clinical trials and in the real world received PD-1/PD-L1 inhibitor.
Authors: Ma Zhiyong , Wang Huijuan , Wei Chunhua , guo Wei Zhang , Yan Xiangtao , Zhang Mina , Zhang Xiaojuan , Niu Yuanyuan , Yang Jinpo
Published: June 2021

e18733

Background: Although PD-1/PD-L1 inhibitors have become the standard treatment for patients with advanced non-small cell lung cancer (NSCLC), data from clinical trials are difficult to be verified in the real world. This study aims to compare the differences in population characteristics, treatment modes and clinical outcomes of advanced NSCLC patients received PD-1/PD-L1 inhibitors between the real-world (RWS) and the clinical study (RCT). Methods: This study enrolled 305 advanced NSCLC patients who received at least one PD-1/PD-L1 inhibitor treatment selected in the Affiliated Cancer Hospital of Zhengzhou University/Henan Cancer Hospital Information System and the Zero Krypton database during January 2016 to September 2019. The patients were divided into RWS group and RCT group. The PD-1/PD-L1 inhibitors included pembrolizumab, sintilizumab, nivolizumab, tislelizumab, carrelizumab, teriprizumab, durvalizumab and Atezolizumab. We performed paired analysis in clinical characteristics and treatment modes. Results: There were 155 cases in the RCT group and 150 cases in the RWS group. The RCT group consisted of higher proportion in male (79.4%) and squamous-carcinoma type (41.3%) than the RWS group, while more patients of brain metastasis (28%) and combination therapy (50.7%) in the RWS group. The ORRs were 42.4% and 20.6% respectively in the RCT and RWS groups receiving first-line treatment with PD-1/PD-L1 inhibitors, and the difference was statistically different. Moreover, the ORRs were 42.4% and 20.6% respectively in the RCT and RWS groups receiving PD-1/PD-L1 inhibitor as second-line treatment, without statistical difference. The progression-free survival (PFS) was 15.5 vs. 13.5 months in the RCT and RWS groups ( P= 0.91), and the median overall survival (OS) was 25.4 vs. 33.8 months respectively ( P= 0.24), with no statistical difference. After propensity match of baseline characteristics of the two groups of patients, it contained 108 patients in the RCT and RWS groups. The PFS was 13.3 vs. 13.3 months in the RCT and RWS groups ( P= 0.47), and the median OS was 21.1 vs. 23.2 months ( P= 0.58), with no statistical difference. Conclusions: Although more female, brain metastases and adenocarcinoma patients receiving PD-1/PD-L1 inhibitors in the real world, the clinical benefits were consistent with those in clinical trials. The results of propensity matching on the baseline characteristics of patients supported this conclusion.
Evaluating real-world overall survival (rwOS) across oncology data sources: Friends of Cancer Research non-small cell lung cancer pilot study.
Authors: Lasiter Laura , Baxi Shrujal , Belli Andrew J. , Boyd Marley , Christian Jennifer , Cohen Aaron B. , Espirito Janet L , Garrett-Mayer Liz , Hansen Eric , Izano Monika A. , Natanzon Yanina , Rivera Donna , Robert Nicholas J. , Small Mackenzie , Sweetnam Connor , Tymejczyk Olga , Wagner Joseph , Allen Jeff
Published: June 2021

e18749

Background: Friends of Cancer Research and five data partners used electronic health record-sourced datasets to conduct parallel analyses in real-world data (RWD). The study assessed estimates of rwOS among patients taking platinum doublet chemotherapy (chemo) or pembrolizumab in combination with chemo (IO+chemo) in first-line treatment for metastatic non-small cell lung cancer (mNSCLC). Methods: The KEYNOTE-189 clinical trial was selected as a reference for cohort selection in the RWD. We applied select available KEYNOTE-189 eligibility criteria to compare rwOS in a homogenous real-world population. Analyses were conducted following a mutually developed statistical analysis plan that was harmonized across data partners. Twelve-month rwOS, and unadjusted and adjusted hazard ratios (HR) for death were calculated using time-to-event methods with patients censored at last structured activity prior to the data cutoff. Results: The five datasets included patients treated with chemo (range of n=155 to 1501) and IO+chemo patients (n=36 to 405, Table). Twelve-month rwOS estimates ranged from 45% to 58% in the chemo arm and 44% to 68% in the IO +chemo arm. The HR for death comparing IO+chemo to chemo varied across groups, ranging from 0.79 (95% CI: 0.68, 0.92) to 1.10 (95% CI: 0.70, 1.72). The HR for death adjusted for age, gender, performance status, and smoking status did not significantly alter results, ranging from 0.80 (95% CI: 0.69, 0.93) to 1.15 (96% CI: 0.71, 1.85). Conclusions: The systematic evaluation of reproducibility and performance of rwOS across five real-world cohorts and the impact of implementing consistent eligibility criteria and methods was useful to understand the consistency of results in real-world populations and relationship between treatments and outcomes in the absence of randomization. A well-articulated research question and a pre-specified analytic plan that includes covariate definitions are necessary preliminary steps to guide data harmonization, standardization, and analysis. A range of observed results highlights the complexity of real-world data, including differences in sample size, underlying patient variability across datasets, and missing covariate data. The harmonization process and observed results underscore the importance of a well-articulated research question and a pre-specified analytic plan to guide data harmonization, standardization, and analysis. [Table: see text]
Facility contextual effects influence the use of adjuvant immunotherapy in stage III melanoma.
Authors: Leonard Laura D. , Torphy Robert J. , Beaty Laurel , de Araujo Thiago B. , Colborn Kathryn , Ho Felix , Albuqueque Arthur , Lewis Karl D. , Gonzalez Rene , Medina Theresa Michelle , McCarter Martin , Stewart Camille L. , Gleisner Ana
Published: June 2021

e18758

Background: There are now numerous effective adjuvant immunotherapy options for surgically resected stage III melanoma including novel checkpoint inhibitors and targeted therapies. Current guidelines recommend that the decision to treat stage III melanoma with adjuvant immunotherapy should be individualized and based upon disease burden, patient goals and anticipated therapy tolerance. We sought to assess the contribution of patient, tumor and facility factors on the implementation of immunotherapy in patients with surgically resected stage III melanoma. Methods: Using the National Cancer Database (NCDB), patients from 2012-2017 that underwent excision and were found to have a positive sentinel node were identified. A multivariable mixed effects logistic regression model with a random intercept for site was used to determine the effect of patient, tumor, and facility variables on the probability of immunotherapy. Reference Effect Measures (REM) were used to estimate the variation in immunotherapy use due to unmeasured facility factors (contextual effects) after adjusting for measured patient, tumor, and facility variables. Results: From 2012 to 2017, the percent of patients with stage III melanoma treated with adjuvant immunotherapy increased from 23.7% to 38.5% (p < 0.05). Overall, younger patients and patients with private insurance were more likely to receive immunotherapy. Tumor factors associated with increased use of adjuvant immunotherapy included increasing depth, mitotic rate ³1, ulceration, lymphovascular invasion (LVI), and undergoing a completion lymph node dissection (CLND). Additionally, treatment at a facility with a surgical volume <190 cases/year was associated with increased immunotherapy use. However, the width of the 90% REM range for unmeasured facility effects exceeded that of the measured facility, tumor, time, and patient demographics suggesting that contextual effects had a higher contribution to the variation in immunotherapy use. Conclusions: Our analysis suggests that uninsured patients and patients with government insurance (Medicaid and Medicare) are not receiving immunotherapy at the same frequency as privately insured patients with the same tumor characteristics treated at the same facility. Lastly, compared to known patient, tumor and facility factors, institutional contextual effects were the major drivers of the implementation of immunotherapy.[Table: see text]
Changes in chronic disease medication adherence following oral anticancer agent initiation in patients with multiple myeloma.
Authors: Gatwood Justin , Dashputre Ankur , Wallace Alex , Gatwood Katie S. , Farris Karen B. , Mackler Emily R. , Rizvi-Toner Amna , Rajpurohit Abhijeet , Farley Joel
Published: June 2021

e18760

Background: Improvements in treatment options for multiple myeloma (MM) have led to double-digit increases in 5-year survival rates over the past 40 years. Such extended survival has increased emphasis for the management of comorbid chronic conditions. Initial analyses suggest that oral anticancer agent (OAA) initiation for MM may correspond to significant reductions in adherence to chronic disease medications. Methods: This was a retrospective cohort study of adults diagnosed with and being treated for MM between 2013-2018 using data from the IBM MarketScan Commercial Claims and Encounters databases and a 20% sample of Medicare claims data. Adults (18 years and older) were included if they were diagnosed with and had at least two claims for an OAA indicated for MM, had continuous enrollment for 12 months both before and after OAA initiation, and were previously diagnosed with two chronic conditions and had prescription fills for select chronic conditions. Medication adherence was determined using the proportion of days covered (PDC) metric and was compared for the 12 months before and after the OAA initiation by Wilcoxon signed-rank tests, McNemar’s tests, and difference-in-differences (DinD) models. Results: A slight majority of the 2,765 patients (total N from both databases) were male (52.3%), and hypertension (94.5%) and hyperlipidemia (69.2%) were the most common comorbid conditions. Mean OAA adherence in the first year of therapy was 55.8% (SD: 23.5) and 63.5% (SD: 26.9) for commercial and Medicare patients, respectively. PDCs for comorbid therapies declined in the first year after OAA initiation, irrespective of payer (table), and the proportion adherent to these therapies (PDC > 80%) also declined consistently. OAA adherence tended to align with the direction of changes in comorbid therapy adherence with those nonadherent to their OAA (PDC < 80%) demonstrating general declines in comorbid therapy PDCs post-OAA initiation (p<0.05 in 4 of 6 DinD models). Conclusions: Among adults with MM and multiple chronic conditions, the pre-OAA initiation level of adherence appears to dictate chronic disease medication use patterns after OAA initiation. The starting of OAA therapy facilitates an opportunity for providers to reinforce the need for total regimen adherence to improve the odds of positive cancer- and non-cancer-related outcomes. [Table: see text]
Retrospective study on the management of patients admitted for febrile neutropenia and considered to be at low risk at the Centre Hospitalier Universitaire de Québec.
Authors: Jean Tommy , Lemieux Julie , Soucy Geneviève , Caron Francis , Leblanc Dominique
Published: June 2021

e18762

Background: Febrile neutropenia is a serious complication of chemotherapy leading to hospitalization in cancer patients. According to a practice guidelines published by ASCO (American Society of clinical Oncology) and IDSA (Infectious Diseases Society of American) in 2018, patients meeting the criteria for low-risk neutropenia according to the MASCC score (Multinational Association for Supportive Care in Cancer Score) could be treated as outpatient and thus avoid hospitalization. The objective of the study was to assess the number and proportion of patients who were hospitalized for febrile neutropenia in university hospital that would have met the low risk criteria of febrile neutropenia. We also wanted to know if these patients had experienced a favorable outcome during hospitalization. Methods: We performed a retrospective study including all patients admitted for febrile neutropenia in 3 hospitals in Quebec City during the period from January 1, 2018 to December 31, 2019. We excluded patients with leukemia, as well as stem cell transplant patients. The chart review retrospectively established the MASCC score for each patient. We also established according to predefined criteria whether the clinical course was favorable or unfavorable. Results: A total of 177 hospitalizations met our inclusion criteria. We found that 101/177 (57.1%) of hospitalized patients met the criteria for low-risk neutropenia according to the MASCC score (score of 21 and above). Of this number 74/177 (41.8%) presented all the criteria suggested for receiving outpatient treatment. In these patients 70/177 (39.5%) presented a favorable evolution during hospitalization and thus 4/177 (2.3%) presented an unfavorable evolution. Among these, 2 patients presented with infections considered major (2 bacteremia), 1 patient developed acute renal failure, and 1 other patient developed delirium. There was no death or admission to the intensive care unit in these 4 patients. Conclusions: According to this retrospective study, about 40% of patients admitted for febrile neutropenia filled the criteria of low risk febrile neutropenia and could be treated as outpatient. Given this represents a significant proportion of patients, a protocol for systematic follow-up of outpatient treatment with low-risk febrile neutropenia should be put in place.
Prevalence of lung cancer in Colombia and a new diagnostic algorithm using health administrative databases: A real-world evidence study.
Authors: Buitrago Giancarlo , Amaya-Nieto Javier , Torres Gabriel Fernando
Published: June 2021

e18764

Background: Reliable, timely and detailed information of lung cancer mortality and costs from low- and middle-income countries is essential to policy design. We aimed to develop an electronic algorithm to identify lung cancer prevalent patient in Colombia using official databases and to estimate prevalence rates by age, sex, and geographic region. Methods: We performed a cross sectional study based on national claim databases in Colombia ( Base de datos de suficiencia de la Unidad de Pago por Capitación and Base de Datos Única de Afiliados) to identify lung cancer prevalent patients in 2017. Several algorithms based on the presence or absence of oncological procedures (Chemotherapy, radiotherapy and surgery), and a minimum number of months that each individual had lung cancer ICD-10 codes in the previous 3 years, were developed. After testing 16 algorithms, those with the closest prevalence rates to the ones reported by aggregated official sources (GLOBOCAN, National Cancer Institute and Cuenta de Alto Costo) were selected . We estimated prevalence rates by age, sex, and geographic region. Results: Two algorithm s were selected: i) it was defined as the presence of ICD-10 codes for 4 months or more (sensitive algorithm); and ii) adding the presence of at least one oncological procedure (specific algorithm). Estimated prevalence rates per 100,000 population were 15.3 and 9.7 for the sensitive and specific algorithms, respectively. These rates were higher in men (9.9), over 65 years old (37.1), who lived in Central and Bogota regions (14.7 and 10.9, respectively) (Table). Conclusions: Selected algorithms showed similar prevalence estimations to those reported by official sources and allowed us to estimate prevalence rates in specific aging, regional and gender groups for Colombia using national claims databases. These findings could be useful to identify clinical and economical outcomes related to lung cancer patients using national individual-level databases. [Table: see text]
Effect of first-line pembrolizumab treatment in individuals with advanced non-small cell lung cancer and poor performance status.
Authors: Veluswamy Rajwanth , Ji Jiayi , Hu Liangyuan , Wang Xiaoliang , Smith Cardinale B. , Kale Minal
Published: June 2021

e18796

Background: There is limited evidence supporting the optimal use of immune checkpoint inhibitors (ICIs) in NSCLC patients with poor performance status (PS), as clinical trials exclude these patients. In this study, we use real-world oncology data to determine the impact of first line pembrolizumab vs. no treatment in high PD(L)-1 expressing cancers in individuals with advanced NSCLC and ECOG PS ≥2. Methods: We performed a retrospective cohort study of patients with advanced NSCLC with ECOG PS ≥2 between 09/01/2014 and 02/18/2020, using the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database. Patients were included if they were PD(L)-1 high (≥50%) and had clinical and treatment information recorded within 90 days of diagnosis. Real-world overall survival (rwOS) was defined as time from diagnosis to death (censored at last EHR activity). Median rwOS was estimated using weighted Kaplan-Meier methods. A marginal Cox structural model with inverse probability of treatment weighting was used to adjust for selection bias and estimate the effectiveness of pembrolizumab. The inverse probability weights were estimated using an ensemble machine learning technique, Super Learner, based on age, gender, race, practice type and smoking history. Adjusted hazard ratios (aHR) were estimated using weighted Cox proportional hazards models. Stratified analysis was conducted by ECOG PS (2 vs >2). Results: 217 (16%) individuals with advanced NSCLC and high PD(L)-1 expression received no treatment, compared to 546 (39%) individuals who received 1L pembrolizumab. The no-treatment group had a lower proportion of ECOG 2 compared to the pembrolizumab group (Table). Median rwOS in the no-treatment group was 2.4 months, compared to 7.1 months in the pembrolizumab group (p<0.001). In unadjusted survival analyses in the entire cohort and in cohorts stratified by ECOG status, treatment with pembrolizumab was associated with a significantly lower risk of death (hazard ratio [HR]: 0.38, 95% Confidence Interval [CI]: 0.31-0.45). In adjusted analyses, individuals treated with pembrolizumab had improved survival (HR: 0.40, 95% CI: 0.35-0.45). Conclusions: Our analysis of real-world clinical oncology data demonstrated that 1L treatment with pembrolizumab was associated with significantly improved rwOS among individuals with ECOG ≥ 2. [Table: see text]
The COVID-19 pandemic led to a reduction in cancer services in Australia.
Authors: Biondi Christine , Milch Vivienne , Nguyen Van , Ryan Regina , Roder David , Woods Alan , Cooper Kristie , Wang Rhona , Anderiesz Cleola , Keefe Dorothy Mary Kate
Published: June 2021

e18812

Background: Australian oncologists reported dramatic decreases in cancer referrals during the pandemic. As real time data were difficult to acquire, Cancer Australia used surrogate measures to infer where reductions in medical services occurred. We analysed data available through the Medicare Benefits Schedule (MBS), a list of the medical services and professional attendances subsidised by the Australian Government, for the five highest incidence cancers: breast, colorectal, lung, prostate, and skin cancers. Methods: We identified over 500 MBS item codes for diagnostic and treatment procedures for malignancies and pre-cancerous conditions. Item codes were categorised into analysis groups based on cancer type and/or similarities in type of service. Data were examined at national and jurisdictional levels for 2020 to determine reductions during the initial COVID-19 period and to monitor subsequent recovery. Data were compared to 2019 to account for normal seasonal variation. Results: Australia’s first wave of the pandemic ran from March to May, and a second wave in the state of Victoria alone ran from July to September 2020. We observed notable reductions across all diagnostic and surgical procedure groups examined, with initial reductions observed between March and April for diagnostic procedures, and a one-month delay for surgical procedures, between April and May. Some services showed an initial recovery in May, with many showing partial or full recovery by June. For some groups, analyses showed sustained reductions over the 12-month period. While COVID-19 case numbers were greater during the second wave, the impact on services was less pronounced, likely owing to more refined policy approaches to managing health system and workforce capacity. There was further recovery by September for some but not all services. Similar patterns of change were observed across all Australian states and territories, with some variation by jurisdiction. Conclusions: The pandemic has impacted the delivery of cancer care. Any potential delays in diagnoses and treatment due to these reductions in services may lead to more advanced cancer stage at diagnosis and poorer patient outcomes including recurrence and survival. Impact of COVID-19 on selected cancer services in Australia in 2020.[Table: see text]
Patient out-of-pocket savings with lower-dose trastuzumab.
Authors: Dreyer Marie S. , Kacew Alec , Hsieh Po-Hung , Serritella Anthony , Knoebel Randall W. , Nanda Rita , Strohbehn Garth William , Ratain Mark J.
Published: June 2021

e18828

Background: Trastuzumab-related costs of human epidermal growth factor receptor 2 (HER2) positive breast cancer treatment are significant, approaching $70,000 per patient in the adjuvant setting alone. Recently developed population pharmacokinetic models demonstrate that therapeutic levels of trastuzumab are maintained despite decreased maintenance dose or dose frequency, potentially improving trastuzumab’s value proposition. In this observational study, we evaluate the potential patient- and health system-level financial implications of low-dose trastuzumab. Methods: We identified 196 individuals who received treatment for HER2-positive breast cancer with trastuzumab or its biosimilars at a single urban comprehensive cancer center between January 1, 2017 and October 31, 2019. We estimate, using publicly available information, patient-experienced out-of-pocket costs using deterministic modeling under different conditions corresponding to changes in dosing practices, geographic site of trastuzumab administration, patient employment status, intent of treatment, and billing procedures, as well as Medicare cost-savings estimates. Results: Both reducing the maintenance dose of trastuzumab from the FDA-labeled dose of 6 mg/kg to 4 mg/kg Q3W and reducing maintenance dose frequency of trastuzumab from 6 mg/kg Q3W to Q4W were each associated with significant patient savings on drug- and administration-related out-of-pocket costs. Depending on billing practice and clinical scenario, patient savings as a percentage of total costs were 9-20% (neoadjuvant), 17-22% (adjuvant), and 14-19% (metastatic) with 6 mg/kg Q4W dosing. Similarly, 4 mg/kg Q3W dosing had savings of 15-25% (neoadjuvant), 19-28% (adjuvant), and 13-28% (metastatic). Utilization of off-label dosing regimens could result in $2.69 billion USD in annual Medicare spending on trastuzumab, an estimated savings of $670-810 million USD. Conclusions: Meaningful patient-level and system-level financial savings in the treatment of HER2-positive breast cancer can be achieved using pharmacokinetically near-equivalent low-dose or reduced frequency maintenance trastuzumab dosing. Given the significant potential savings, further prospective studies aimed at reducing dose or frequency of monoclonal antibodies in the treatment of cancer are warranted.