Socioeconomic Status, Palliative Care, and Death at Home Among Patients With Cancer Before and During COVID-19.

Importance: The COVID-19 pandemic had a profound impact on the delivery of cancer care, but less is known about its association with place of death and delivery of specialized palliative care (SPC) and potential disparities in these outcomes. Objective: To evaluate the association of the COVID-19 pandemic with death at home and SPC delivery at the end of life and to examine whether disparities in socioeconomic status exist for these outcomes. Design, Setting, and Participants: In this cohort study, an interrupted time series analysis was conducted using Ontario Cancer Registry data comprising adult patients aged 18 years or older who died with cancer between the pre-COVID-19 (March 16, 2015, to March 15, 2020) and COVID-19 (March 16, 2020, to March 15, 2021) periods. The data analysis was performed between March and November 2023. Exposure: COVID-19-related hospital restrictions starting March 16, 2020. Main Outcomes and Measures: Outcomes were death at home and SPC delivery at the end of life (last 30 days before death). Socioeconomic status was measured using Ontario Marginalization Index area-based material deprivation quintiles, with quintile 1 (Q1) indicating the least deprivation; Q3, intermediate deprivation; and Q5, the most deprivation. Segmented linear regression was used to estimate monthly trends in outcomes before, at the start of, and in the first year of the COVID-19 pandemic. Results: Of 173 915 patients in the study cohort (mean [SD] age, 72.1 [12.5] years; males, 54.1% [95% CI, 53.8%-54.3%]), 83.7% (95% CI, 83.6%-83.9%) died in the pre-COVID-19 period and 16.3% (95% CI, 16.1%-16.4%) died in the COVID-19 period, 54.5% (95% CI, 54.2%-54.7%) died at home during the entire study period, and 57.8% (95% CI, 57.5%-58.0%) received SPC at the end of life. In March 2020, home deaths increased by 8.3% (95% CI, 7.4%-9.1%); however, this increase was less marked in Q5 (6.1%; 95% CI, 4.4%-7.8%) than in Q1 (11.4%; 95% CI, 9.6%-13.2%) and Q3 (10.0%; 95% CI, 9.0%-11.1%). There was a simultaneous decrease of 5.3% (95% CI, -6.3% to -4.4%) in the rate of SPC at the end of life, with no significant difference among quintiles. Patients who received SPC at the end of life (vs no SPC) were more likely to die at home before and during the pandemic. However, there was a larger immediate increase in home deaths among those who received no SPC at the end of life vs those who received SPC (Q1, 17.5% [95% CI, 15.2%-19.8%] vs 7.6% [95% CI, 5.4%-9.7%]; Q3, 12.7% [95% CI, 10.8%-14.5%] vs 9.0% [95% CI, 7.2%-10.7%]). For Q5, the increase in home deaths was significant only for patients who did not receive SPC (13.9% [95% CI, 11.9%-15.8%] vs 1.2% [95% CI, -1.0% to 3.5%]). Conclusions and Relevance: These findings suggest that the COVID-19 pandemic was associated with amplified socioeconomic disparities in death at home and SPC delivery at the end of life. Future research should focus on the mechanisms of these disparities and on developing interventions to ensure equitable and consistent SPC access.

HER2-Mutant Advanced and/or Metastatic Non-Small-Cell Lung Cancer: A US Electronic Health Records Database Analysis of Clinical Characteristics, Treatment Practice Patterns, and Outcomes.

BACKGROUND: Real-world data for advanced/metastatic non-small-cell lung cancer (NSCLC) with mutations in human epidermal growth factor 2 (HER2) are scarce. We aimed to assess treatment patterns and outcomes among patients with HER2-mutant advanced/metastatic NSCLC. PATIENTS AND METHODS: This retrospective nationwide electronic health record study evaluated patient characteristics, treatment patterns, treatment duration, and overall survival for adults with HER2-mutant advanced/metastatic NSCLC without epidermal growth factor receptor mutation. RESULTS: Of 55 included patients, median (quartile 1 [Q1]-quartile 3 [Q3]) age was 63.0 (58.0-72.0) years, 42 (76%) were women, and 39 (71%) were current/former smokers. In first-line therapy, 14 regimens were used for median (Q1-Q3) duration of 3.1 (2.4-6.2) months, with most patients (n = 39, 71%) receiving platinum-based chemotherapy alone or in combination with other agents. Median (95% CI) overall survival from first-line treatment initiation was 19.0 (12.2-not estimable) months, with no significant association with age, sex, or smoking status. Thirty-five (64%) patients received second-line therapy for median (Q1-Q3) duration of 3.3 (2.0-5.2) months. Fourteen second-line regimens were used; most commonly immunotherapy alone or in combination with other agents (n = 16, 46%). Sixteen (46%) patients received third-line therapy for median (Q1-Q3) duration of 1.9 (1.3-2.7) months. Nine third-line regimens were used, with 7 (44%) patients receiving HER2-directed agents. CONCLUSION: First- and second-line treatments for HER2-mutant NSCLC varied widely and treatment duration was short. The approval of trastuzumab deruxtecan for NSCLC supports wider HER2 testing to identify eligible patients for HER2-directed therapy.

Healthcare costs, resource utilization, and productivity loss associated with colorectal cancer screening.

OBJECTIVES: To evaluate healthcare costs, resource utilization, associated costs, and lost productivity for colorectal cancer (CRC) screening in an average-risk population. METHODS: This retrospective cohort study identified average-risk individuals (50-75 years) with claims in the Optum Research Database for CRC screening test between 1 January 2014 to 31 December 2018. Index date was defined as the first date of a claim for colonoscopy, fecal immunochemical test (FIT), guaiac-based fecal occult blood test (FOBT) or multi-target stool DNA test (mt-sDNA). Screening costs were evaluated with descriptive statistics and multivariable analyses, adjusting for patient characteristics and index screening costs. RESULTS: In total, 903,831 individuals were identified by test groups: mt-sDNA (n = 29,614), FIT (n = 254,002), guaiac-based FOBT (n = 112,757) and colonoscopy (n = 507,458). Adjusted costs for index screening were, colonoscopy ($3,029), mt-sDNA ($752), FIT ($45), and (FOBT ($153). Adjusted costs across the six months following the index screening were $146 for colonoscopy, $329 for mt-sDNA, $306 for FIT, and $412 for FOBT. Colonoscopy had the highest costs for lost productivity. CONCLUSIONS: Screening colonoscopy had the highest productivity loss and healthcare costs up-front, suggesting potential cost benefits for noninvasive screening modalities. The more frequent screening interval required for FIT and FOBT resulted in a higher yearly cost than colonoscopy or mt-sDNA.

Colorectal cancer (CRC) is a prominent healthcare concern the United States, which accounted for 149,500 new cases and 52,980 deaths in 2021. Screening is effective for diagnosing the condition at earlier more treatable stages, and reducing deaths. However, screening is largely underutilized in part due to perceived cost barriers. This observational study used insurance claims data to calculate healthcare costs, resource use, and lost productivity for CRC screening in an average-risk population aged 50­75 years. A total of 903,831 individuals were identified by test groups: multi-target stool DNA test (mt-sDNA test; 29,614 individuals), fecal immunochemical test (FIT; 254,002 individuals), guaiac-based fecal occult blood test (FOBT; 112,757 individuals) and colonoscopy (507,458 individuals). Adjusted costs for initial screening were $3,029 for colonoscopy, $752 for mt-sDNA, $45 for FIT, and $153 for FOBT. Adjusted colonoscopy-related costs combined across the six months following the initial screening were $146 for the colonoscopy cohort, $329 for mt-sDNA, $306 for FIT, and $412 for FOBT. Colonoscopy had the highest costs for lost productivity. Overall, screening colonoscopy was accompanied by the highest productivity loss and up-front costs, suggesting potential cost benefits for noninvasive screening modalities ­ mt-sDNA, FIT, and FOBT; however, the more frequent screening interval required by FIT and FOBT resulted in a higher estimated average yearly screening cost.

Association of Circulating Tumor DNA Testing Before Tissue Diagnosis With Time to Treatment Among Patients With Suspected Advanced Lung Cancer: The ACCELERATE Nonrandomized Clinical Trial.

Importance: Liquid biopsy has emerged as a complement to tumor tissue profiling for advanced non-small cell lung cancer (NSCLC). The optimal way to integrate liquid biopsy into the diagnostic algorithm for patients with newly diagnosed advanced NSCLC remains unclear. Objective: To evaluate the use of circulating tumor DNA (ctDNA) genotyping before tissue diagnosis among patients with suspected advanced NSCLC and its association with time to treatment. Design, Setting, and Participants: This single-group nonrandomized clinical trial was conducted among 150 patients at the Princess Margaret Cancer Centre-University Health Network (Toronto, Ontario, Canada) between July 1, 2021, and November 30, 2022. Patients referred for investigation and diagnosis of lung cancer were eligible if they had radiologic evidence of advanced lung cancer prior to a tissue diagnosis. Interventions: Patients underwent plasma ctDNA testing with a next-generation sequencing (NGS) assay before lung cancer diagnosis. Diagnostic biopsy and tissue NGS were performed per standard of care. Main Outcome and Measures: The primary end point was time from referral to treatment initiation among patients with advanced nonsquamous NSCLC using ctDNA testing before diagnosis (ACCELERATE [Accelerating Lung Cancer Diagnosis Through Liquid Biopsy] cohort). This cohort was compared with a reference cohort using standard tissue genotyping after tissue diagnosis. Results: Of the 150 patients (median age at diagnosis, 68 years [range, 33-91 years]; 80 men [53%]) enrolled, 90 (60%) had advanced nonsquamous NSCLC. The median time to treatment was 39 days (IQR, 27-52 days) for the ACCELERATE cohort vs 62 days (IQR, 44-82 days) for the reference cohort (P < .001). Among the ACCELERATE cohort, the median turnaround time from sample collection to genotyping results was 7 days (IQR, 6-9 days) for plasma and 23 days (IQR, 18-28 days) for tissue NGS (P < .001). Of the 90 patients with advanced nonsquamous NSCLC, 21 (23%) started targeted therapy before tissue NGS results were available, and 11 (12%) had actionable alterations identified only through plasma testing. Conclusions and Relevance: This nonrandomized clinical trial found that the use of plasma ctDNA genotyping before tissue diagnosis among patients with suspected advanced NSCLC was associated with accelerated time to treatment compared with a reference cohort undergoing standard tissue testing. Trial Registration: ClinicalTrials.gov Identifier: NCT04863924.

Symptom screening with Targeted Early Palliative care (STEP) versus usual care for patients with advanced cancer: a mixed methods study.

PURPOSE: Although early palliative care is recommended, resource limitations prevent its routine implementation. We report on the preliminary findings of a mixed methods study involving a randomized controlled trial (RCT) of Symptom screening with Targeted Early Palliative care (STEP) and qualitative interviews. METHODS: Adults with advanced solid tumors and an oncologist-estimated prognosis of 6-36 months were randomized to STEP or symptom screening alone. STEP involved symptom screening at each outpatient oncology visit; moderate to severe scores triggered an email to a palliative care nurse, who offered referral to in-person outpatient palliative care. Patient-reported outcomes of quality of life (FACT-G7; primary outcome), depression (PHQ-9), symptom control (ESAS-r-CS), and satisfaction with care (FAMCARE P-16) were measured at baseline and 2, 4, and 6 months. Semi-structured interviews were conducted with a subset of participants. RESULTS: From Aug/2019 to Mar/2020 (trial halted due to COVID-19 pandemic), 69 participants were randomized to STEP (n = 33) or usual care (n = 36). At 6 months, 45% of STEP arm patients and 17% of screening alone participants had received palliative care (p = 0.009). Nonsignificant differences for all outcomes favored STEP: difference in change scores for FACT-G7 = 1.67 (95% CI: -1.43, 4.77); ESAS-r-CS = -5.51 (-14.29, 3.27); FAMCARE P-16 = 4.10 (-0.31, 8.51); PHQ-9 = -2.41 (-5.02, 0.20). Sixteen patients completed qualitative interviews, describing symptom screening as helpful to initiate communication; triggered referral as initially jarring but ultimately beneficial; and referral to palliative care as timely. CONCLUSION: Despite lack of power for this halted trial, preliminary results favored STEP and qualitative results demonstrated acceptability. Findings will inform an RCT of combined in-person and virtual STEP.

Patient and provider factors associated with colorectal cancer screening among average risk health plan enrollees in the US, 2015-2018.

BACKGROUND: To assess patient and primary care provider (PCP) factors associated with adherence to American Cancer Society (ACS) and United States Preventive Services Task Force (USPSTF) guidelines for average risk colorectal cancer (CRC) screening. METHODS: Retrospective case-control study of medical and pharmacy claims from the Optum Research Database from 01/01/2014 - 12/31/2018. Enrollee sample was adults aged 50 - 75 years with ≥ 24 months continuous health plan enrollment. Provider sample was PCPs listed on the claims of average-risk patients in the enrollee sample. Enrollee-level screening opportunities were based on their exposure to the healthcare system during the baseline year. Screening adherence, calculated at the PCP level, was the percent of average-risk patients up to date with screening recommendations each year. Logistic regression modelling was used to examine the association between receipt of screening and enrollee and PCP characteristics. An ordinary least squares model was used to determine the association between screening adherence among the PCP's panel of patients and patient characteristics. RESULTS: Among patients with a PCP, adherence to ACS and USPSTF screening guidelines ranged from 69 to 80% depending on PCP specialty and type. The greatest enrollee-level predictors for CRC screening were having a primary/preventive care visit (OR = 4.47, p < 0.001) and a main PCP (OR = 2.69, p < 0.001). CONCLUSIONS: Increased access to preventive/primary care visits could improve CRC screening rates; however, interventions not dependent on healthcare system contact, such as home-based screening, may circumvent the dependence on primary care visits to complete CRC screening.

Dysregulating PHO Signaling via the CDK Machinery Differentially Impacts Energy Metabolism, Calcineurin Signaling, and Virulence in Cryptococcus neoformans.

Fungal pathogens uniquely regulate phosphate homeostasis via the cyclin-dependent kinase (CDK) signaling machinery of the phosphate acquisition (PHO) pathway (Pho85 kinase-Pho80 cyclin-CDK inhibitor Pho81), providing drug-targeting opportunities. Here, we investigate the impact of a PHO pathway activation-defective Cryptococcus neoformans mutant (pho81Δ) and a constitutively activated PHO pathway mutant (pho80Δ) on fungal virulence. Irrespective of phosphate availability, the PHO pathway was derepressed in pho80Δ with all phosphate acquisition pathways upregulated and much of the excess phosphate stored as polyphosphate (polyP). Elevated phosphate in pho80Δ coincided with elevated metal ions, metal stress sensitivity, and a muted calcineurin response, all of which were ameliorated by phosphate depletion. In contrast, metal ion homeostasis was largely unaffected in the pho81Δ mutant, and Pi, polyP, ATP, and energy metabolism were reduced, even under phosphate-replete conditions. A similar decline in polyP and ATP suggests that polyP supplies phosphate for energy production even when phosphate is available. Using calcineurin reporter strains in the wild-type, pho80Δ, and pho81Δ background, we also demonstrate that phosphate deprivation stimulates calcineurin activation, most likely by increasing the bioavailability of calcium. Finally, we show that blocking, as opposed to permanently activating, the PHO pathway reduced fungal virulence in mouse infection models to a greater extent and that this is most likely attributable to depleted phosphate stores and ATP, and compromised cellular bioenergetics, irrespective of phosphate availability. IMPORTANCE Invasive fungal diseases cause more than 1.5 million deaths per year, with an estimated 181,000 of these deaths attributable to Cryptococcal meningitis. Despite the high mortality, treatment options are limited. In contrast to humans, fungal cells maintain phosphate homeostasis via a CDK complex, providing drug-targeting opportunities. To investigate which CDK components are the best targets for potential antifungal therapy, we used strains with a constitutively active (pho80Δ) and an activation-defective (pho81Δ) PHO pathway, to investigate the impact of dysregulated phosphate homeostasis on cellular function and virulence. Our studies suggest that inhibiting the function of Pho81, which has no human homologue, would have the most detrimental impact on fungal growth in the host due to depletion of phosphate stores and ATP, irrespective of phosphate availability in the host.

Specialist Palliative Care Referral Practices Among Oncologists, Cardiologists, Respirologists: A Comparison of National Survey Studies.

CONTEXT: Although patients with nonmalignant diseases have palliative care needs similar to those of cancer patients, they are less likely to receive specialist palliative care (SPC). Referral practices of oncologists, cardiologists, and respirologists could provide insight into reasons for this difference. OBJECTIVES: We compared referral practices to SPC among cardiologists, respirologists, and oncologists, discerned from surveys (the Canadian Palliative Cardiology/Respirology/Oncology Surveys). METHODS: Descriptive comparison of survey studies; multivariable linear regression analysis of association between specialty and referral frequency. Surveys for each specialty were disseminated to physicians across Canada in 2010 (oncologists) and 2018 (cardiologists, respirologists). RESULTS: The combined response rate of the surveys was 60.9% (1568/2574): 603 oncologists, 534 cardiologists, and 431 respirologists. Perceived availability of SPC services was higher for cancer than for noncancer patients. Oncologists were more likely to make a referral to SPC for a symptomatic patient with a prognosis of

Early palliative care and quality of dying and death in patients with advanced cancer.

OBJECTIVE: Early palliative care (EPC) in the outpatient setting improves quality of life for patients with advanced cancer, but its impact on quality of dying and death (QODD) and on quality of life at the end of life (QOL-EOL) has not been examined. Our study investigated the impact of EPC on patients' QODD and QOL-EOL and the moderating role of receiving inpatient or home palliative care. METHOD: Bereaved family caregivers who had provided care for patients participating in a cluster-randomised trial of EPC completed a validated QODD scale and indicated whether patients had received additional home palliative care or care in an inpatient palliative care unit (PCU). We examined the effects of EPC, inpatient or home palliative care, and their interactions on the QODD total score and on QOL-EOL (last 7 days of life). RESULTS: A total of 157 caregivers participated. Receipt of EPC showed no association with QODD total score. However, when additional palliative care was included in the model, intervention patients demonstrated better QOL-EOL than controls (p=0.02). Further, the intervention by PCU interaction was significant (p=0.02): those receiving both EPC and palliative care in a PCU had better QOL-EOL than those receiving only palliative care in a PCU (mean difference=27.10, p=0.002) or only EPC (mean difference=20.59, p=0.02). CONCLUSION: Although there was no association with QODD, EPC was associated with improved QOL-EOL, particularly for those who also received inpatient care in a PCU. This suggests a long-term benefit from early interdisciplinary palliative care on care throughout the illness. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (#NCT01248624).

Colorectal screening among average risk individuals in the United States, 2015-2018.

Colorectal cancer screening rates are important metrics for public health and quality indicators for health care systems; however, published estimates of colorectal cancer screening rates often include both high-risk and average-risk patients, and the use of different epidemiologic methods makes between-study comparisons tenuous. The objective of this study was to measure the proportion of average-risk American adults who are up to date with colorectal cancer screening guidelines and examine the impact of evaluation methods on screening rate estimates. This repeated cross-sectional study used administrative claims to identify individuals aged 50-75 years between 2015 and 2018 with ≥ 1-year of continuous health plan enrollment. Sensitivity analyses to replicate prior studies in the literature included: 1) retrospective cohort study requiring ≥ 10 years of continuous enrollment to identify the most current screening rates (2018), and 2) inclusion of individuals with higher colorectal cancer risk. A total of 2,579,898; 2,948,064; 3,312,882; and 2,752,864 individuals were included in the 2015, 2016, 2017, and 2018 populations, respectively. In the cross-sectional sample, the proportion of individuals with up-to-date colorectal cancer screening was 51.8%, 51.3%, 51.0%, and 51.1% in 2015, 2016, 2017, and 2018, respectively. The inclusion of high-risk individuals increased estimates approximately 37%. Using a retrospective cohort design, 67.5% of average-risk individuals were up to date in 2018. This study demonstrated the impact of methodological differences on rate estimates. Efforts to track screening rates require transparency in measurement methods to accurately evaluate progress in improving rates.

Family physicians' involvement in palliative cancer care.

BACKGROUND: Family physicians' (FPs) long-term relationships with their oncology patients position them ideally to provide primary palliative care, yet their involvement is variable. We examined perceptions of FP involvement among outpatients receiving palliative care at a cancer center and identified factors associated with this involvement. METHODS: Patients with advanced cancer attending an oncology palliative care clinic (OPCC) completed a 25-item survey. Eligible patients had seen an FP within 5 years. Binary multivariable logistic regression analyses were conducted to identify factors associated with (1) having seen an FP for palliative care within 6 months, and (2) having a scheduled/planned FP appointment. RESULTS: Of 258 patients, 35.2% (89/253) had seen an FP for palliative care within the preceding 6 months, and 51.2% (130/254) had a scheduled/planned FP appointment. Shorter travel time to FP (odds ratio [OR] = 0.67, 95% confidence interval [CI] = 0.48-0.93, p = 0.02), the FP having a 24-h support service (OR = 1.96, 95% CI = 1.02-3.76, p = 0.04), and a positive perception of FP's care (OR = 1.05, 95% CI = 1.01-1.09, p = 0.01) were associated with having seen the FP for palliative care. English as a first language (OR = 2.90, 95% CI = 1.04-8.11, p = 0.04) and greater ease contacting FP after hours (OR = 1.33, 95% CI = 1.08-1.64, p = 0.008) were positively associated, and female sex of patient (OR = 0.51, 95% CI = 0.30-0.87, p = 0.01) and travel time to FP (OR = 0.66, 95% CI = 0.47-0.93, p = 0.02) negatively associated with having a scheduled/planned FP appointment. Number of OPCC visits was not associated with either outcome. CONCLUSION: Most patients had not seen an FP for palliative care. Accessibility, availability, and equity are important factors to consider when planning interventions to encourage and facilitate access to FPs for palliative care.

Plasma-first: accelerating lung cancer diagnosis and molecular profiling through liquid biopsy.

Introduction: Molecular profiling of tumor tissue is the gold standard for treatment decision-making in advanced non-small cell lung cancer (NSCLC). Results may be delayed or unavailable due to insufficient tissue, prolonged wait times for biopsy, pathology assessment and testing. We piloted the use of plasma testing in the initial diagnostic workup for patients with suspected advanced lung cancer. Methods: Patients with ⩽15 pack-year smoking history and suspected advanced lung cancer referred to the lung cancer rapid diagnostic program underwent plasma circulating-tumor DNA testing using a DNA-based mutation panel. Tissue testing was performed per standard of care, including comprehensive next-generation sequencing (NGS). The primary endpoint was time from diagnostic program referral to cancer treatment in stage IV NSCLC patients (Cohort A) compared to a contemporary cohort not enrolled in the study (Cohort B) and an historical pre-COVID cohort referred to the program between 2018 and 2019 (Cohort C). Results: From January to June 2021, 20 patients were enrolled in Cohort A; median age was 70.5 years (range 33-87), 70% were female, 55% Caucasian, 85% never smokers, and 75% were diagnosed with NSCLC. Seven had actionable alterations detected in plasma or tissue (4/7 concordant). Fusions, not tested in plasma, were identified by immunohistochemistry for three patients. Mean result turnaround time was 17.8 days for plasma NGS and 23.6 days for tissue (p = 0.10). Mean time from referral to treatment initiation was significantly shorter in cohort A at 32.6 days (SD 13.1) versus 62.2 days (SD 31.2) in cohort B and 61.5 days (SD 29.1) in cohort C, both p < 0.0001. Conclusion: Liquid biopsy in the initial diagnostic workup of patients with suspected advanced NSCLC can lead to faster molecular results and shorten time to treatment even with smaller DNA panels. An expansion study using comprehensive NGS plasma testing with faster turnaround time is ongoing (NCT04862924).

Public interest in medical assistance in dying and palliative care.

OBJECTIVES: Medical assistance in dying (MAiD) is legal in an increasing number of countries, but there are concerns that its availability may compromise access to palliative care. We assessed public interest in MAiD, palliative care, both, or neither, and examined characteristics associated with this interest. METHODS: We surveyed a representative sample of the adult Canadian public, accessed through a panel from May to June 2019. Weighted generalised multinomial logistic regression analyses were used to determine characteristics associated with interest in referral to palliative care, MAiD, or both, in the event of diagnosis with a serious illness. RESULTS: Of 1362 participants who had heard of palliative care, 611 (44.8% weighted (95% CI 42.1% to 47.5%)) would be interested in both MAiD and palliative care, 322 (23.9% (95% CI 21.5% to 26.2%)) palliative care alone, 171 (12.3% (95% CI 10.5% to 14.1%)) MAiD alone and 258 (19.0% (95% CI 16.9% to 21.2%)) neither. In weighted multinomial logistic regression analyses, interest in both MAiD and palliative care (compared with neither) was associated with better knowledge of the definition of palliative care, older age, female gender, higher education and less religiosity; interest in palliative care alone was associated with better knowledge of the definition of palliative care, older age, female gender and being married/common law; interest in MAiD alone was associated with less religiosity (all p<0.05). CONCLUSIONS: There is substantial public interest in potential referral to both MAiD and palliative care. Simultaneous availability of palliative care should be ensured in jurisdictions where MAiD is legal, and education about palliative care should be a public health priority.

The economic value of liquid biopsy for genomic profiling in advanced non-small cell lung cancer.

Background: Liquid biopsy (LB) can detect actionable genomic alterations in plasma circulating tumor circulating tumor DNA beyond tissue testing (TT) alone in advanced non-small cell lung cancer (NSCLC) patients. We estimated the cost-effectiveness of adding LB to TT in the Canadian healthcare system. Methods: A cost-effectiveness analysis was conducted using a decision analytic Markov model from the Canadian public payer (Ontario) perspective and a 2-year time horizon in patients with treatment-naïve stage IV non-squamous NSCLC and ⩽10 pack-year smoking history. LB was performed using the comprehensive genomic profiling Guardant360™ assay. Standard of care TT for each participating institution was performed. Costs and outcomes of molecular testing by LB + TT were compared to TT alone. Transition probabilities were calculated from the VALUE trial (NCT03576937). Sensitivity analyses were undertaken to assess uncertainty in the model. Results: Use of LB + TT identified actionable alterations in more patients, 68.5 versus 52.7% with TT alone. Use of the LB + TT strategy resulted in an incremental cost savings of $3065 CAD per patient (95% CI, 2195-3945) and a gain in quality-adjusted life-years of 0.02 (95% CI, 0.01-0.02) versus TT alone. More patients received chemo-immunotherapy based on TT with higher overall costs, whereas more patients received targeted therapy based on LB + TT with net cost savings. Major drivers of cost-effectiveness were drug acquisition costs and prevalence of actionable alterations. Conclusion: The addition of LB to TT as initial molecular testing of clinically selected patients with advanced NSCLC did not increase system costs and led to more patients receiving appropriate targeted therapy.

Upfront Next Generation Sequencing in Non-Small Cell Lung Cancer.

In advanced non-small cell lung cancer (NSCLC), patients with actionable genomic alterations may derive additional clinical benefit from targeted treatment compared to cytotoxic chemotherapy. Current guidelines recommend extensive testing with next generation sequencing (NGS) panels. We investigated the impact of using a targeted NGS panel (TruSight Tumor 15, Illumina) as reflex testing for NSCLC samples at a single institution. Molecular analysis examined 15 genes for hotspot mutation variants, including AKT1, BRAF, EGFR, ERBB2, FOXL2, GNA11, GNAQ, KIT, KRAS, MET, NRAS, PDGFRA, PIK3CA, RET and TP53 genes. Between February 2017 and October 2020, 1460 samples from 1395 patients were analyzed. 1201 patients (86.1%) had at least one variant identified, most frequently TP53 (47.5%), KRAS (32.2%) or EGFR (24.2%). Among these, 994 patients (71.3%) had clinically relevant variants eligible for treatment with approved therapies or clinical trial enrollment. The incremental cost of NGS beyond single gene testing (EGFR, ALK) was CAD $233 per case. Reflex upfront NGS identified at least one actionable variant in more than 70% of patients with NSCLC, with minimal increase in testing cost. Implementation of NGS panels remains essential as treatment paradigms continue to evolve.

Automating Access to Real-World Evidence.

Introduction: Real-world evidence is important in regulatory and funding decisions. Manual data extraction from electronic health records (EHRs) is time-consuming and challenging to maintain. Automated extraction using natural language processing (NLP) and artificial intelligence may facilitate this process. Whereas NLP offers a faster solution than manual methods of extraction, the validity of extracted data remains in question. The current study compared manual and automated data extraction from the EHR of patients with advanced lung cancer. Methods: Previously, we extracted EHRs from 1209 patients diagnosed with advanced lung cancer (stage IIIB or IV) between January 2015 and December 2017 at Princess Margaret Cancer Centre (Toronto, Canada) using the commercially available artificial intelligence engine, DARWEN (Pentavere, Ontario, Canada). For comparison, 100 of 333 patients that received systemic therapy were randomly selected and clinical data manually extracted by two trained abstractors using the same accepted gold standard feature definitions, including patient, disease characteristics, and treatment data. All cases were re-reviewed by an expert adjudicator. Accuracy and concordance between automated and manual methods are reported. Results: Automated extraction required considerably less time (<1 day) than manual extraction (∼225 person-hr). The collection of demographic data (age, sex, diagnosis) was highly accurate and concordant with both methods (96%-100%). Accuracy (for either extraction approach) and concordance were lower for unstructured data elements in EHR, such as performance status, date of diagnosis, and smoking status (NLP accuracy: 88%-94%; Manual accuracy: 78%-94%; concordance: 71%-82%). Concurrent medications (86%-100%) and comorbid conditions (96%-100%), were reported with high accuracy and concordance. Treatment details were also accurately captured with both methods (84%-100%) and highly concordant (83%-99%). Detection of whether biomarker testing was performed was highly accurate and concordant (96%-98%), although detection of biomarker test results was more variable (accuracy 84%-100%, concordance 84%-99%). Features with syntactic or semantic variation requiring clinical interpretation were extracted with slightly lower accuracy by both NLP and manual review. For example, metastatic sites were more accurately identified through NLP extraction (NLP: 88%-99%; manual: 71%-100%; concordance: 70%-99%) with the exception of lung and lymph node metastases (NLP: 66%-71%; manual: 87%-92%; concordance: 58%) owing to analogous terms used in radiology reports not being included in the accepted gold standard definition. Conclusions: Automated data abstraction from EHR is highly accurate and faster than manual abstraction. Key challenges include poorly structured EHR and the use of analogous terms beyond the accepted gold standard definition. The application of NLP can facilitate real-world evidence studies at a greater scale than could be achieved with manual data extraction.

Impact of early palliative care according to baseline symptom severity: Secondary analysis of a cluster-randomized controlled trial in patients with advanced cancer.

BACKGROUND: Early palliative care (EPC) improves the quality of life but may not be feasible for all patients with advanced cancer. Symptom screening has been suggested to triage patients for EPC, but scant evidence exists for this practice. METHODS: We conducted a subgroup analysis of a cluster-randomized controlled trial of EPC vs. standard oncology care according to patients' baseline symptom scores (high [>23] vs. low [≤23] Edmonton Symptom Assessment System Distress Score [ESAS SDS]). A linear mixed-effects model was used to account for correlation within clusters, adjusting for the baseline outcome score and all covariates in the original trial. RESULTS: Among the 461 participants, baseline symptom scores were high in 229 patients (127 intervention, 102 control) and low in 232 (101 intervention and 131 control). Among those with high baseline symptoms, there was improved quality of life in the EPC arm compared to controls at 4 months (adjusted difference in primary outcome of FACIT-Sp change score [95% CI], 8.7 [2.8 to 14.5], p = 0.01; adjusted difference in QUAL-E, 4.2 [0.9-7.5], p = 0.02); there was also improved satisfaction with care (6.9 [3.8-9.9], p = 0.001) and clinician-patient interactions (-1.7 [-3.4 to -0.1], p = 0.04), but no significant difference in ESAS SDS (-5.6 [-12.7 to 1.4], p = 0.11). In the low baseline symptom group, there were no significant differences between arms for any outcomes. CONCLUSION: EPC improved quality of life, satisfaction with care, and clinician-patient interactions only in those with high baseline symptoms. Symptom severity may be an appropriate criterion to trigger early referrals to palliative care.

Effects of Ethnicity on Outcomes of Patients With EGFR Mutation-Positive NSCLC Treated With EGFR Tyrosine Kinase Inhibitors and Surgical Resection.

INTRODUCTION: In addition to the higher prevalence of EGFR mutations found among lung cancer cases in East Asian patients, it is unclear whether there are differences in treatment outcomes by ethnicity-that is, East Asian versus non-East Asian. METHODS: Patients diagnosed with EGFR-mutant lung cancer between January 2004 and October 2014 at a single center were reviewed. Data captured included demographics, tumor and treatment information, and survival. Survival of patients of East Asian and non-East Asian ancestry was compared, including in the subgroup that received EGFR tyrosine kinase inhibitor (TKI) for advanced disease and in those with early-stage disease that underwent surgical resection. RESULTS: A total of 348 patients with EGFR-mutant NSCLC were identified. There was a higher proportion of nonsmokers among those of East Asian ethnicity. No significant difference in survival was seen between patients of East Asian and non-East Asian ethnicity, median 6.7 years (95% confidence interval [CI]: 5.4-not applicable) and 5.4 years (95% CI: 4.1-7.2), respectively (p = 0.09). Among 196 patients that received treatment with EGFR TKI, the median survival from TKI initiation was also similar for those of East Asian and non-East Asian ethnicity, 3.0 years (95% CI: 2.1-3.5) and 2.7 years (95% CI: 2.2-3.5), respectively. Among the early-stage patients that underwent surgical resection (n = 163), those of East Asian ethnicity had similar median recurrence-free survival from surgery compared with non-East Asian patients, 5.3 years (95% CI: 3.5-not applicable) and 5.1 years (95% CI: 3.3-7.2), respectively. CONCLUSIONS: In a cohort of patients with EGFR-mutant lung cancer with access to uniform standards of care, East Asian ethnicity was not associated with improved survival after treatment with EGFR TKI or surgical resection.

Healthcare costs related to adverse events in hepatocellular carcinoma treatment: A retrospective observational claims study.

BACKGROUND: Hepatocellular carcinoma (HCC) is an aggressive form of liver cancer with increasing incidence and mortality worldwide. For metastatic disease, systemic treatment is recommended. In addition to tumor characteristics, adverse events (AEs) may influence regimen choice. AIM: To analyze healthcare burden among patients with advanced HCC, by treatment type and AEs observed. METHODS: Included were adult commercial and Medicare Advantage enrollees with ≥2 non-diagnostic claims coded for HCC (the first setting the index date); ≥1 claim for systemic treatment of advanced/metastatic HCC; and continuous enrollment for a 6-month pre-index baseline period to ≥1 month post-index (follow-up). Patients were excluded by lack of systemic treatment; incomplete demographic information; pregnancy, liver transplant, other cancers during baseline or clinical trial participation. We describe patient characteristics, common AEs, overall survival, and healthcare burden in 2017 USD up to 12 months after initiation of tyrosine kinase inhibitor (TKI) monotherapy; immune checkpoint inhibitor (ICI) monotherapy; or FOLFOX combination therapy. RESULTS: The analytic sample consisted of 322 patients (median age 65.8 years, 76% male) who had 12 months' (unless death occurred prior) available follow-up, with median follow-up of 9 months. Among these, 241 (75%) had TKI monotherapy, 23 (7%) had ICI monotherapy, and 58 had FOLFOX (18%) first-line treatment. Overall, patients had a high burden of AEs (mean 3.2), with the most prevalent being pain (75%), infection (39%), ascites (34%), and bleeding (29%). After adjusting for covariates, infection ($50 374), fever ($47 443), and diarrhea ($29 912) imposed the highest incremental annual costs versus patients without the AE. Up to 90% of costs were attributable to inpatient admissions, with 56% to 60% involving intensive care. Median 1-year survival was 32%. CONCLUSIONS: This real-world study demonstrated AE burden in alignment with previous clinical studies. Regardless of regimen used, AEs are associated with substantial healthcare costs due to inpatient care.

Phase II Trial of Symptom Screening With Targeted Early Palliative Care for Patients With Advanced Cancer.

BACKGROUND: Routine early palliative care (EPC) improves quality of life (QoL) for patients with advanced cancer, but it may not be necessary for all patients. We assessed the feasibility of Symptom screening with Targeted Early Palliative care (STEP) in a phase II trial. METHODS: Patients with advanced cancer were recruited from medical oncology clinics. Symptoms were screened at each visit using the Edmonton Symptom Assessment System-revised (ESAS-r); moderate to severe scores (screen-positive) triggered an email to a palliative care nurse, who called the patient and offered EPC. Patient-reported outcomes of QoL, depression, symptom control, and satisfaction with care were measured at baseline and at 2, 4, and 6 months. The primary aim was to determine feasibility, according to predefined criteria. Secondary aims were to assess whether STEP identified patients with worse patient-reported outcomes and whether screen-positive patients who accepted and received EPC had better outcomes over time than those who did not receive EPC. RESULTS: In total, 116 patients were enrolled, of which 89 (77%) completed screening for ≥70% of visits. Of the 70 screen-positive patients, 39 (56%) received EPC during the 6-month study and 4 (6%) received EPC after the study end. Measure completion was 76% at 2 months, 68% at 4 months, and 63% at 6 months. Among screen-negative patients, QoL, depression, and symptom control were substantially better than for screen-positive patients at baseline (all P<.0001) and remained stable over time. Among screen-positive patients, mood and symptom control improved over time for those who accepted and received EPC and worsened for those who did not receive EPC (P<.01 for trend over time), with no difference in QoL or satisfaction with care. CONCLUSIONS: STEP is feasible in ambulatory patients with advanced cancer and distinguishes between patients who remain stable without EPC and those who benefit from targeted EPC. Acceptance of the triggered EPC visit should be encouraged. CLINICALTRIALS: gov identifier: NCT04044040.