bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of patient reported outcomes (PROs) completion patterns in patients with cancer: Examining real-world data.
Authors: Al-Antary Nada , Adjei Boakye Eric , Tam Samantha , Wilson Carl , Poisson Laila , Zatirka Theresa , Ryan Michael , Hirko Kelly , Chang Steven S. , Movsas Benjamin
Published: June 2023

6609

Background: Use of Patient Reported Outcomes (PROs) in clinical practice plays a major role in improving care, quality of life, hospitalization, emergency room visits and consequently improving overall survival. However, robust information on real-time assessment of PROs in cancer patients is insufficient, as most available data are limited to specific populations enrolled in clinical trials. This thereby increases disparities among minorities of race, age, and socioeconomic status, creating a barrier between the benefits of PROs and these underserved populations. This study examines the response rates, patterns and characteristics of patients completing PROs in a tertiary cancer center. Methods: Patients with a cancer diagnosis and an oncologic provider visit at a tertiary cancer center were offered an opportunity to complete Patient Reported Outcome Measures (PROMs) between August 2020 and July 2022.We used the National Institute of Health’s computer adaptive tests Patient-Reported Outcomes Measurement Information System (PROMIS) instruments in pain interference, physical function, fatigue, and depression. Seven days prior to their clinical appointment, patients were assigned the PROMIS instruments in MyChart, then offered in-clinic completion with a tablet at check-in, if not completed online. A decision tree model was employed to assess the factors that may influence patients' PROMs completion (age, gender, race, marital status, insurance, stage, comorbidity score, and provider specialty and location). Results: A total of 8,535 patients were offered the PROMIS CAT version 2.0 instrument during the study period. The two most important factors that determine whether a patient completed PROMs in order of importance were provider specialty and patient race. Patients were more likely to complete PROMs if they had a visit with a provider in Radiation Oncology (RC) or Surgery specialty compared with Medicine or Supportive Oncology specialty (40.86% versus 29.68%). Among patients who had a visit with a provider in RC or Surgery specialty, there was a better chance of PROMs completion with White race compared to Black or Other races (45.83% versus 33.69%). Of those who had a visit with a provider in Medicine or Supportive Oncology specialty, there was a better chance of PROMs completion with Other or White races compared to Black race (32.40% versus 22.19%). Conclusions: We found that provider specialty and patient race were the most important factors influencing patients’ PROMs completion. In order to realize the full benefit of PROs in patient care, multilevel interventions can be employed to increase patient-provider utilization of PROs. Moreover, efforts should focus on a patient-centered design to address patient and provider barriers impeding PROs accessibility and completion.
Molecular diagnostic classification for cancers of unknown primary (CUP): Post-testing diagnosis and treatment impact analysis from real-world claims data.
Authors: Rivers Zachary , Huey Ryan W , Ben-Shachar Rotem , Avadhani Anjali Narayan , Taxter Timothy J. , Beauchamp Kyle A. , Hockenberry Adam J , Nimeiri Halla , Allam Joelle , Kalyan Aparna , Raghav Kanwal Pratap Singh , Lee Michael Sangmin
Published: June 2023

6610

Background: Next-generation sequencing-based molecular diagnostic classifiers can help identify the tissue of origin for CUP, and enable the selection of site-specific therapies (as opposed to empiric chemotherapy) for this vulnerable population with high unmet need. NCCN guidelines do not endorse the use of tissue of origin classifiers as standard of care for CUP patients due to limited clinical evidence. Here, we linked results of a commercial molecular diagnostic classifier with claims data to understand how this test impacted patient care. Methods: We assessed de-identified claims data from the Komodo Healthcare Map (a database including provider visits, laboratory tests, procedures, imaging, and prescriptions) linked to the Tempus Tumor Origin (TO) test—a machine learning classifier that uses RNA-seq data to classify tumors into one of 68 histological subtypes. Eligible patients had pathologist-confirmed CUP and were classified as one of 9 subtypes (each having n>10). Impact was determined by identifying either one or more new diagnostic codes or new subtype-related medication claims following TO testing. Results: We analyzed data from 490 patients: 483 for the diagnosis analysis and 213 for the medication analysis (206 patients appear in both, due to differences in timing of diagnosis vs. medication claims). We found that post-TO testing, 49.9% (n=241) of patients had a diagnostic code change, 63.8% (n=136) had a treatment change, and 41% (n=85) had both. In total, 59.6% (n=292) of patients were impacted by the use of this classifier, with variation according to predicted subtype (Table). Cancer types with specific treatment options were more likely to have changes in diagnostic code or treatment. For CUP predicted as lung adenocarcinomas, 85% of the cases had a new subtype-aligned medication, and 78% were specifically placed on immunotherapy (IO) compared with 24% of overall patients. Conclusions: Using real-world claims data, we show that molecular diagnostic testing utilizing Tempus TO impacted care for a majority of CUP patients. This cohort will be followed to identify how TO testing decisions impact outcomes. [Table: see text]
Patient reported outcomes (PROs) collection modalities among patients diagnosed with cancer: Online vs in-person.
Authors: Adjei Boakye Eric , Wilson Carl , Zatirka Theresa , Tam Samantha , Al-Antary Nada , Nair Mrudula , Poisson Laila , Hirko Kelly , Ryan Michael , Chang Steven S. , Movsas Benjamin
Published: June 2023

6612

Background: Patient reported outcomes (PRO) can be valuable clinical tools to embed the voice of patients into the clinical assessment. PROs provide important metrics to guide treatment decision making, improve quality of life, reduce acute care, and extend survival in cancer patients. Different modalities for collecting patient reported outcome measures (PROMs) exist (e.g., electronic, paper, telephone); yet little is known about factors associated with PROMs completion modality. More information on PROMs completion modality may determine addressable barriers. We sought to determine whether patients’ sociodemographic and clinical factors differed by completion modality. Methods: Beginning in 2021 all patients diagnosed with cancer who had a visit with an oncologic provider at a tertiary cancer center were assigned the National Institute of Health’s computer adaptive tests Patient-Reported Outcomes Measurement Information System (PROMIS) instruments in pain interference, physical function, fatigue, and depression through the MyChart patient portal 7 days prior to the visit. If this was not completed at the time of the visit, it was available for completion on a tablet during check-in. The outcome variable was completion modality defined as the method a patient used to complete their PROMs (MyChart vs. In-Person). Multivariable logistic regression model was used to estimate the association between patients’ sociodemographic and clinical factors (age, sex, race/ethnicity, marital status, insurance type, stage, provider specialty) and completion modality. Results: A total of 2915 patients completed PROMs, of which 54% completed using MyChart and 46% completed in-person. The average age of patients was 59.6 (SD=12.4) years, most were females (63.1%), White (69.4%) and married (59.2%). Compared to male patients, females were less likely to complete PROMs in-person (aOR=0.80, 0.67–0.95). However, patients were more likely to complete PROMs in-person if they were of Black race (aOR=1.85, 1.52–2.24) or Other race (aOR=1.48, 1.12–1.96) vs. White; single (aOR=1.30, 1.05–1.62) vs. married; or have Medicaid/other insurance (aOR=1.52, 1.15–2.01) vs. private insurance. Patients who had visits with a radiation oncology provider (aOR=1.50, 1.20–1.86) or surgical oncology provider (aOR=1.32, 1.07–1.62) were more likely to complete PROMs in-person compared to those who had visits with a medical oncology provider. Conclusions: Almost half of the patients completed PROMs in-person during check-in, which was unexpected in the context of trends toward mobile-based patient engagement. Patients in underserved populations were the most likely to complete PROMs in-person. Although offering PROMs remotely may be more efficient and allow monitoring between visits, offering an in-person option helps to capture PROs from underserved populations.
An application of extrapolating clinical data from single-arm trials to assess comparative effectiveness.
Authors: Suh Kangho , Ramsey Scott David , Kang Ashley , Ko Gilbert , Williamson Todd E. , Liao Nick , Sullivan Sean D.
Published: June 2023

6614

Background: Single arm studies pose some challenges to determining comparative effectiveness of treatments. Such is the case with the tumor agnostic tropomyosin receptor kinase (TRK) inhibitors, larotrectinib and entrectinib. Larotrectinib and entrectinib are indicated for treatment of advanced cancer in patients (pts) with NTRK gene fusions. Lacking head-to-head trials, modeling methods are useful to estimate relative benefit. A direct naïve comparison, where single arms from separate trials are compared, can be used. Here, we estimate and compare long term benefit for pts receiving larotrectinib or entrectinib for NTRK gene fusion-positive non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) by extrapolating survival curves to generate expected life-years (LYs) and quality-adjusted life-years (QALYs). Methods: We used partitioned survival methods to forecast comparative effectiveness. Larotrectinib survival data were derived from an updated July 2021 analysis of 21 adults (≥18 years of age) with NSCLC and 15 pts with CRC (NCT02122913, NCT02637687, and NCT02576431). Survival data for entrectinib were derived from published literature. Extrapolation of results were necessary to estimate long-term outcomes since the mean follow-up was less than three years. Progression free survival and overall survival for both treatments were estimated using several parametric survival distributions (Exponential, Weibull, Log-logistic, and Log-normal), then selecting based on AIC and clinical plausibility. QALYs were estimated by adjusting the time spent in the pre progression and post progression health states by utility values from the literature. A discount rate of 3% was applied to LYs and QALYs. Model uncertainty was evaluated using one-way and probabilistic sensitivity analyses. Results: In the larotrectinib trials, response rates were 86% and 33% in NSCLC and CRC, respectively. Exponential curves were fit for both treatments. In the entrectinib trials, response rates were 70% in NSCLC and 29% in CRC. The larotrectinib model estimated 7.3 LYs (95% Credible Interval [CrI]: 3.3, 11.4) and 4.3 QALYs (95% CrI: 2.2, 6.5) in NSCLC and 1.7 LYs (95% CrI: 0.8, 3.2) and 1.3 QALYs (95% CrI: 0.7, 2.3) in CRC. The entrectinib model estimated 2.7 LYs (95% CrI: 1.7, 4.2) and 1.6 QALYs (95% CrI: 1.1, 2.3) in NSCLC and 0.5 LYs (95% CrI: 0.2, 1.6) and 0.4 QALYs (95% CrI: 0.1, 1.1). Compared to entrectinib, larotrectinib produced additional gains of 4.7 LYs and 2.7 QALYs in NSCLC and 1.1 LYs and 0.9 QALYs in CRC. Limitations include non-matched baseline differences in the trial populations. Conclusions: In the absence of head-to-head trials, comparative effectiveness can be assessed by extrapolating from single armed studies indicated for the same patient population. Larotrectinib improved survival and quality adjusted survival vs entrectinib. Additional studies are needed to confirm these findings.
Real world utilization and disparities in outcome in the use of novel anti-androgen agents for metastatic prostate cancer.
Authors: Hirani Samina , Durojaiye Ashimiyu , He Jian , Sabo Roy T. , Paul Asit K.
Published: June 2023

6616

Background: Despite advances in treatment, disparities exist in prostate cancer treatment and utilization of treatment resources based on several factors including race and socioeconomic status. As evidence-based guidelines increasingly define novel androgen receptor inhibitors (ARIs) as the standard of care, it is important to understand how the utilization of ARIs impacts the outcome. In this study, we investigated the relationship between the utilization of the two most commonly used ARIs, Abiraterone and Enzalutamide, and survival among patients with metastatic prostate cancer. Methods: We conducted a retrospective analysis of patients in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database from January 1st, 2013 to December 31, 2017. All patients aged 18 years and above with metastatic prostate cancer were included. The objective of these study was to determine the utilization of ARIs in different groups (age, race, location, income status and marital status) and investigate the impact of these variables on the survival. Kaplan-Meir survival curves were used for the survival analysis. Patients were stratified by: who received an ARI alone or in combination vs. who did not. Log-rank tests were used to compare the stratified survival probability curves by groups. A multivariate proportional hazards model was used to compare the instantaneous risk of death in metastatic prostate cancer between patients based on selected covariates. All hypothesis tests were two-tailed with a p-value < 0.05 considered statistically significant. Results: A total of 5889 patients with metastatic prostate cancer were included in the analysis. The median age was 73 years; 39% of patients received an ARI alone or in combination with other agents. Among the patients who received ARIs, 77 %, 15% and 8% were white, black and of other races, respectively. Use of ARIs were more in urban locations (98.1% vs. 1.9% at rural locations) and in patients with higher and mid-level incomes (73.0% vs. 22.7% in low-income group). While survivals were inferior in all subgroups of patients who did not receive ARIs, survivals was better in white race (vs. black and others) as well as in younger age group who received ARIs. However, in the latter group, there was no statistical difference in survival in rural vs. urban locations and low income vs. high and mid-income groups. Conclusions: Our study shows that 39% of patients with metastatic prostate cancer in the SEER Medicare population utilized an ARI.There was a significant underutilization of ARIs in non-white, rural locations and low-income subgroup. White race and younger age populations were associated with better survival irrespective of use of ARIs. Among patients who did not receive ARIs, survivals were inferior in rural (vs. urban) and low-income (vs. high and mid-income) patients, but survivals were equivalent in these subgroups who received ARIs.
An indirect comparison of elranatamab’s (ELRA) objective response rate (ORR) from MagnetisMM-3 (MM-3) vs real-world external control arms in triple-class refractory (TCR) multiple myeloma (MM).
Authors: Costa Luciano J. , LeBlanc Thomas William , Tesch Hans , Sonneveld Pieter , Kyle Ryan , Sinyavskaya Liliya , Hlavacek Patrick , Meche Aster , Ren Jinma , Schepart Alex , Aydin Didem , DiBonaventura Marco
Published: June 2023

6618

Background: ELRA is a BCMAxCD3 bispecific antibody being investigated for the treatment of R/R MM. The phase 2 MM-3 trial was single-armed; the aim of this study (NCT05565391) was to contextualize the efficacy data from MM-3 with two real-world (RW) external control arms. Methods: A retrospective cohort study was conducted to indirectly compare the efficacy observed in MM-3 Cohort A (BCMA-naïve; N=123) from the 9-month data cut with two US-based oncology electronic health record databases, Flatiron Health (FH) and COTA, as external controls. MM-3 inclusion (eg, prior MM diagnosis, ECOG≤2, refractory to ≥1 PI, ≥1 IMiD, and ≥1 anti-CD38) and exclusion (I/E) criteria (eg, plasma cell leukemia, smoldering MM) were applied to each RW database to obtain comparable patient populations across sources. After imposing MM-3 I/E criteria, comparisons between data sources on ORR were conducted by estimating rate ratios (RRs) using log-binomial regression models (unweighted analysis). RRs were also estimated using both inverse probability treatment weighting (IPTW) and augmented IPTW (doubly robust) analyses to account for key covariates (eg, age, comorbidities, ECOG, ISS, prior lines/refractoriness, cytogenetic risk, extramedullary disease, lab values). Results: The 123 patients from MM-3 Cohort A were compared with the 152 and 233 patients identified from the FH and COTA databases, respectively. Treatment regimens in the RWD sources included various combinations of PIs, IMiDs, and mAbs, among other agents (eg, selinexor). Across unweighted, IPTW, and doubly robust analyses, the ORR for ELRA was significantly higher than treatments used for TCR MM patients from RWD sources (Table; all p<.05). Conclusions: Among TCR MM patients who resemble those of the MM-3 trial, ELRA showed improved ORR compared with treatments currently used in clinical practice. [Table: see text]
Endoscopist volume and the quality of colonoscopy of the Korean National Cancer Screening Program.
Authors: Kim Dong Jun , Yoon Nan-He , Kim Seongju , Kim Ji Eun , Lee Hooyeon
Published: June 2023

6627

Background: The Korean government established the National Cancer Screening Program (KNCSP). The KNCSP has provided annual faecal immunochemical test (FIT) for adults aged 50 years or older, and colonoscopy or a double-contrast barium enema test to those with positive results from the FIT. High-quality screening colonoscopy is mandatory to achieve maximum possible CRC prevention. The case volume has been shown to correlate with outcomes in surgical specialties. In contrast, relevant data on colonoscopy is limited. This study aimed to assess the quality indicators of organized CRC screening according to annual colonoscopy volume using KNCSP data. Methods: We used the KNCSP data from 2018 to 2020, which accounted for 378,354 colonoscopy examinations. We used cancer registration data of an extended health insurance program using ICD-11 codes (C18-20). A total of 12,109 CRC patients were registered within 1 year of the date of colonoscopy. We calculated the annual number of colonoscopy examinations by an individual endoscopist. We excluded endoscopists who had a very low or high number of examinations with the highest 1% or lowest 1% as outliers. The final number of endoscopists was 16,552 and colonoscopy examinations were 331,231 during 2018–2020. The annual colonoscopy volume by individual endoscopists was divided into four groups (2–12, 13–24, 25–36, and 37 or more examinations). Multiple linear regression analysis was performed to confirm the association between test accuracy indicators and colonoscopy frequency using a generalized linear model (GLM). We calculated the estimates of the rates for each indicator by adjusting the year. Results: The positive and false positive rates, sensitivity, specificity, and positive predictive value were 4.09%, 1.07%, 83.53%, 98.93%, and 74.68%, respectively. The cancer detection and interval cancer rates were 30.53‰ and 6.29‰, respectively. Quality indicators were related to the annual colonoscopy volume of the endoscopist. Endoscopists with a higher annual colonoscopy volume were more likely to have higher sensitivity, specificity, and positive predictive value than those with a lower annual colonoscopy volume. Endoscopists with higher annual colonoscopy volumes were more likely to have lower positive rates, cancer detection rates, false positive rates, and interval cancers rate than those with lower annual colonoscopy volumes. Conclusions: This study found that the annual volume of colonoscopy examinations was associated with better colonoscopy quality in an organized CRC screening program. A high colonoscopy load could be a sign of substantial experience and lead to better outcomes, as has been shown for surgery. The relationship between quality indicators and case volume is logical and plausible; therefore, more research is required to determine the number of cases that need to be performed in a year to adequately maintain high colonoscopy quality.
Real-world study of treatment patterns and clinical outcomes in patients with metastatic non-small cell lung cancer (mNSCLC) post-approval of immunotherapy in the community oncology setting.
Authors: Spira Alexander I. , Korytowsky Beata , Gao Sara , Dubois Renard , Wilson Thomas , Osterland Andrew , Shi Junxin , Conkling Paul R.
Published: June 2023

6629

Background: Clinical outcomes in patients with mNSCLC have improved post-approval of immunotherapy (IO). However, limited real-world data exists describing the evolution of treatment patterns and impact on outcomes in later lines of therapy (LOT). Here we describe the treatment landscape and outcomes of patients with mNSCLC without driver mutations within community oncology settings. Methods: This retrospective observational study included adult patients with mNSCLC who initiated first LOT (LOT1) for mNSCLC in the US Oncology Network from 1/1/2015 to 12/31/2020 (followed through 3/31/2022), using structured electronic health records. Patients who initiated LOT1 with a targeted therapy or EGFR/ALK/ROS1 inhibitor during any LOT were excluded. Second, third, and fourth LOT (LOT2, LOT3, LOT4) were assigned using start and stop dates. Treatment patterns up to LOT4 were summarized descriptively by period of treatment initiation (early-IO period: 2015–2017; post-IO period: 2018–2020). Overall survival (OS) and time to next treatment (TTNT) were assessed by LOT using Kaplan-Meier analysis. Results: Overall, 11,035 patients met study criteria, of which 3,835 (35%) patients initiated LOT2, 1,264 (11%) patients initiated LOT3, and 393 (4%) patients initiated LOT4 between 2015 and 2020, respectively. From 2015–2017 to 2018–2020, pembrolizumab plus platinum chemotherapy with pemetrexed or paclitaxel as LOT1 increased from 3% (n = 176) to 42% (n = 2,448), and pembrolizumab monotherapy increased from 9% (n = 465) to 26% (n = 1,518). In patients who initiated LOT2, IO followed by docetaxel ± ramucirumab increased from 1% (n = 15) to 15% (n = 295), whereas this sequence from LOT2 to LOT3 was used in 23% (n = 111) from 2015–2017 and 20% (n = 159) from 2018–2020. Median (95% CI) OS was 13.3 (12.6, 14.0) months vs. 14.7 (13.8, 15.3) months from initiation of LOT1 in 2015–2017 vs. 2018–2020, respectively (P = 0.187). Clinical outcomes by LOT and period of treatment initiation are presented as median (95% CI) in the table below. Conclusions: Understanding evolving treatment patterns in the community oncology setting is important for uncovering opportunities for mNSCLC treatment optimization. This descriptive study reveals the increasing use of mono- and combination IO followed by docetaxel ± ramucirumab in the community setting. Additionally, longer OS was noted in the post-IO period, suggesting possible extended benefits from earlier LOT. [Table: see text]
Racial disparities in hospitalization outcomes among patients with cholangiocarcinoma.
Authors: Jackson Inimfon , Ibodeng Gogo-Ogute , Guarin Geneva , Dourado Claudia M.
Published: June 2023

6631

Background: Studies have reported on the rising incidence and mortality outcomes among patients diagnosed with cholangiocarcinoma (CCA) but racial disparities in outcomes among inpatients have not been explored in this population. We examined the racial disparities in outcomes among adult hospitalized patients with a diagnosis of CCA. Methods: Retrospective cohort analyses were conducted using data from the National Inpatient Sample (NIS), 2016-2020. Multivariate logistic and linear regression models were used to examine the association between race/ethnicity and patient disposition, length of stay, elective admissions, and total hospital charges. Results: In the adjusted analyses, while Black patients had 14% higher odds (95% Confidence Interval (CI): 1.04–1.25) of being discharged to a facility/home with home health care versus routine discharge when compared to their White counterparts, Hispanics had 14% lower odds (95% CI: 0.79–0.95). Black patients had 39% higher risk (95% CI: 1.19–1.63) of death versus routine discharge relative to the White patients. Compared to White patients, Blacks (AOR: 1.23; 95% CI: 1.13–1.34), Hispanics (AOR: 1.15; 1.06–1.25) and other race/ethnicities (AOR: 1.20; 1.10–1.31) were more likely to have a length of hospital stay greater than 5 days relative to 5 days or less. Hispanics (β: $16,789; 95% CI: $11,480–$22,099) were found to have higher total hospital charges when compared to the White CCA patients. Additionally, Black (AOR: 0.68; 95% CI: 0.60–0.78) and Hispanic patients (AOR: 0.87; 95% CI: 0.77–0.99) were less likely to be admitted electively to the hospital. Conclusions: Despite advances made in treatment of patients with CCA, the prognosis remains poor. We report disparities in various hospitalization outcomes among adult patients with a diagnosis of CCA. Health care providers need to be aware that these disparities exist and health policies should be implemented to narrow the gap in existing disparities. [Table: see text]
Estimated life-years gained and resultant cost savings from follow-up colonoscopy after a positive multi-target stool DNA (mt-sDNA) test for colorectal cancer screening in commercially insured and Medicare populations.
Authors: Fendrick A. Mark , Kisiel John B. , Ebner Derek W. , Vahdat Vahab , Ozbay A. Burak , Estes Chris , Limburg Paul J.
Published: June 2023

6642

Background: Although follow up colonoscopy (COL) after a positive stool-based colorectal cancer (CRC) screening test is necessary to complete the CRC screening process, follow-up COL rates remain suboptimal, especially among underserved populations. As of January 2023, federal policies require commercial insurers and Medicare to eliminate out of pocket costs for follow-up COL. To estimate the implications of this policy change, we compared the clinical and fiscal outcomes for a simulated cohort receiving a follow-up COL after a non-invasive CRC test ($0 cost sharing), compared to the same cohort not completing follow-up COL (status quo). Methods: Using the validated CRC-AIM model, we simulated a cohort of 6 million average-risk individuals who received mt-sDNA (commercial patients at age 45 and Medicare patients at age 65) and further analyzed only the population with positive mt-sDNA. Life-years gained, CRC incidence, CRC-related mortality and total costs of care (inclusive of CRC screening and treatment) were calculated for a cohort that underwent follow-up COL and compared these outcomes to that same cohort that did not complete follow-up COL. The cost of follow-up COL was assumed to be $1,576 for Medicare and $3,086 for commercially insured patients ($0 out of pocket costs for all). Results: Patients undergoing follow-up COL after a positive mt-sDNA experienced more life-years (83 per 1,000 commercially insured patients and 80 per 1,000 Medicare beneficiaries) compared to those who did not undergo follow-up COL. The follow-up COL resulted in reductions in CRC incidence and CRC mortality by 14% and 16% for commercial and 19% and 23% for Medicare beneficiaries, respectively. Compared to those patients with a mt-sDNA positive test result and did not complete follow-up COL, the total cost per patient for those receiving follow-up COL was $3,339 less for commercially insured ($15,690 – no follow up vs. $12,351 – follow up) and $4,382 less for Medicare beneficiaries ($19,337 – no follow up vs. $14,955 – follow up). Total spending for patients receiving follow-up COL was cost-saving when compared to no follow-up as long as the COL costs were less than $6,269 for commercial plans and $5,753 for Medicare. Conclusions: Completing a follow-up COL after a positive mt-sDNA screening saves lives, enhances equity, and lowers total expenditures. Thus, health care stakeholders should invest in efforts to identify and reduce barriers that ultimately lead to an increase uptake of this potentially lifesaving and cost-reducing intervention.
Association of early completion of portable medical orders with inpatient costs at end-of-life for patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).
Authors: LoCastro Marissa , Baran Andrea M. , Liesveld Jane , Huselton Eric , Loh Kah Poh , Mendler Jason
Published: June 2023

6645

Background: Patients with hematologic malignancies receive more aggressive care at end-of-life (EOL) compared to patients with solid tumors. Costs of care in patients with hematologic malignancies at EOL are high, particularly in the inpatient setting. We previously found that early completion of portable medical orders [termed medical orders for life sustaining treatment (MOLST) in New York state] is associated with less intense care at EOL for patients with AML and MDS. Thus, we hypothesized that early MOLST completion would also be associated with lower inpatient costs at EOL among patients with AML and MDS. Methods: We previously conducted a retrospective study of 358 adults patients with AML or MDS treated at Wilmot Cancer Institute and its affiliated sites who died between January 1, 2014, and December 31, 2019. Of these, 271 patients were eligible for cost analysis. Cost of inpatient care received at the University of Rochester Medical Center (URMC) within the last 30 days of life was obtained from our Finance Decision Support Department. Patients were excluded if inpatient costs at EOL were unavailable. Results: Mean age of patients was 69 years (N=271, range 20-95); 84% (n=227) of patients were hospitalized within 30 days of death. One-third (34%, n=93) of patients completed a MOLST early (>30 days prior to death) whereas 66% (n=178) either did not complete a MOLST or completed a MOLST late (less than or equal to 30 days prior to death). Mean and median inpatient cost of care for all patients at EOL was $39,284 and $19,703, respectively. The rate of hospitalization was lower for patients who completed a MOLST early vs late/never (73.1% vs 90.5%, respectively; p=0.0003), although there was no difference in the number of inpatient visits between the two groups (median=1 visit in both groups; p=0.23). In addition, median cost of inpatient care was lower for patients who completed a MOLST early vs late/never ($10,673 vs $23,177, respectively; p<0.0001). After adjusting for age, sex, and diagnosis, there was a trend toward lower EOL costs in patients completing a MOLST early (p=0.07). Conclusions: In patients with AML or MDS, early MOLST completion may be associated with lower inpatient costs at EOL. Viewing MOLST completion as a surrogate for a goals-of-care discussion, it follows that interventions aimed to increase the frequency of early goals-of-care discussions, advanced care planning, and MOLST completion are likely to improve quality of care and decrease costs at EOL in these patient populations.
A health economic model to assess the impact of prehabilitation on hospital cost savings in gastrointestinal cancer, modelled on English National Health Service tariff.
Authors: Zamora Talaya Bernarda Zamora , Moorthy Krishna , Savva Katerina , Ni Melody
Published: June 2023

6648

Background: Prehabilitation is increasingly being recognised as a high-priority intervention to improve physical and psychological health in cancer patients, prevent treatment-related functional decline and to reduce the incidence and severity of post-surgical complications. The aim of this study is to develop a health economic (HE) model to evaluate the impact of prehabilitation in patients undergoing gastrointestinal cancer surgery. Methods: The objective of the HE model is to estimate the impact of prehabilitation on reducing treatment costs. Data was extracted from systematic reviews and meta-analysis on the effects of prehabilitation in gastrointestinal cancer surgery to identify: i) treatment pathway, ii) prehabilitation components (nutrition/exercise/psychological intervention), and iii) effects on three study outcomes (length of hospital stay, reduction of post-operative complications, and reduced Intensive Care Unit (ICU) stay). The modelling study accounts for the number of hospital admissions and unit costs from NHS hospitals, including cost per bed-day from NHS Reference costs 2017-18 and complication costs and ICU cost from NHS Reference National Cost Schedule 2019-20. Double counting has been corrected to account for the compounded effects on length of stay and complications. The HE model considers the average effect of each study outcome and their confidence intervals. This provides a range of potential impact of prehabilitation in terms of cost reduction based on NHS tariff. Results: Patient weighted average cost savings from prehabilitation was £785, excluding ICU costs. Breakdown of cost savings include £178.6 from reduced length of hospital stay, £214.8 and £434.5 cost savings originating from reductions in minor and major complications, respectively (excluding ICU complication costs). ICU cost savings from prehabilitation were £1,620. For the NHS, based on 237,000 annual surgical procedures, this amounts up to £186,082,321 in cost savings, from a reduction in complications and 421,840 hospital days, and £52,761,227 from ICU stay. Conclusions: In addition to the impact on post-operative complications and hospital stay, this study has demonstrated that prehabilitation results in significant costs savings to healthcare systems. The cost savings are largely from a reduction in the incidence and severity of post-operative complications. The latter contributing to reduced ICU costs.
Superior outcomes after allogeneic stem cell transplantation (SCT) among patients (Pts) ≥ 60 years (yrs) treated with cladribine (CLAD), low dose cytarabine (LDAC) plus venetoclax (Ven) for newly diagnosed acute myeloid leukemia (AML).
Authors: Senapati Jayastu , Kantarjian Hagop M. , Bazinet Alexandre , Reville Patrick Kevin , Borthakur Gautam , Daver Naval Guastad , Dinardo Courtney Denton , Bataller Alex , Jabbour Elias , Short Nicholas James , Popat Uday R. , Alousi Amin Majid , Shpall Elizabeth J. , Garcia-Manero Guillermo , Ravandi Farhad , Kadia Tapan M.
Published: June 2023

7047

Background: CLAD/LDAC/VEN alternating with AZA-VEN has shown promising outcomes in older pts with AML ( Kadia, JCO Nov 2022). Improved disease control and preserved performance status achieved with CLAD/LDAC/VEN treatment, may translate into superior post-SCT outcomes. Methods: We compared outcomes of pts ≥ 60 yrs of age treated on the phase II study of CLAD-LDAC-VEN who underwent SCT in 1st remission (CR1) to a retrospective cohort of pts ≥ 60 yrs treated with hypomethylating agent (HMA)-VEN based or intensive (INT) therapy who underwent SCT in CR1 between 2013-2022. Relapse free survival (RFS) was from response to relapse/death & overall survival (OS) from start of therapy to death. Results: 35 pts treated with CLAD-LDAC-VEN were compared to 42 pts treated with INT & 40 pts with HMA-VEN therapy for remission induction prior to SCT at our center (Table). The median age of pts in the low-intensity arms were similar (68 yrs), but lower on the INT arm (62 yrs). More pts post INT therapy received a myeloablative conditioning (MAC). At a median follow up of 17+ months (m) for CLAD-LDAC-VEN arm, 59 m for INT arm, and 30 m for HMA arm, the median RFS (NR vs. 50 m vs. 20 m respectively, p <0.01) and OS (NR vs. 58 m vs. 32 m respectively, p < 0.01) was superior for the CLAD-LDAC-VEN arm. 3-yr cumulative incidence of relapse & NRM (as competing events) were both significantly lower with CLAD-LDAC-VEN (4% and 7%) compared to INT (17% and 23%) or HMA-VEN (41% and 27%) therapy. Conclusions: Older pts with AML proceeding to SCT after CLAD-LDAC-VEN therapy had significantly improved survival, characterized by significantly lower rates of NRM and relapse compared to HMA-VEN or INT therapies. Larger studies and longer follow up is needed to confirm its benefit. [Table: see text]
Effects of ruxolitinib and magrolimab on calreticulin in myelofibrosis CD34+ cells in vitro: Proof of concept for combination therapy.
Authors: Rinaldi Ciro Roberto , Boasman Kristian , Simmonds Matthew
Published: June 2023

7064

Background: In solid tumours, calreticulin (CALR) overexpression produces a pro-phagocytic signal and is counteracted by concomitant expression of anti- phagocytic CD47, reflecting an apoptosis vs survival mechanism. We have previously found that CD47, not CALR, is overexpressed on the membrane of patients with MPN. Anti-CD47 Magrolimab, is currently being evaluated in clinical trials in AML, MDS but have yet to be tested, either in monotherapy or in combination in MF. Methods: Mononuclear cells were collected by Ficoll separation from bone marrow of 6 MF patients and from 2 controls. CD34+ cells and monocytes were purified using Dynabeads kits from Thermofisher. Cells expression of CALR and CD47 was measured by flow cytometry, before and after incubation with ruxolitinib (Jak inhibitor) alone and in combination with magrolimab. Cells survival was calculated after combining CD34 with monocytes. Informed Consent was obtained for all samples collected. Results: CD47 membrane expression was 57% in untreated MF cells compared to 12% in the control samples and CALR membrane expression was 51.8% in untreated MF cell compared to 12.5% in the control samples. After incubation with ruxolitinib, MF CD34+ cell survival decreased to 98.2%. Following Incubation with magrolimab alone, MF CD34+ cells show no changes in survival (100% alive). The combination of ruxolitinib and magrolimab reduced slightly the MF CD34+ cell survival to 92%. A substantial membrane overexpression of CALR was observed in MF CD34+ cells when incubated with Ruxo and Magrolimab, 74.1%, vs Ruxo alone 52.6%, Magrolimab alone 53.4% and in untreated (51.8%). Interestingly, in the healthy controls, the exposure to combination therapy did not cause the same degree of CALR overexpression (20.7% vs 12.5%), indicating a much stronger pro-phagocytic effect following magrolimab/ruxolitinib combo in MF cancer cells. Conclusions: In vitro, treatment with ruxolitinib or ruxolitinib plus magrolimab, slightly reduce the overall cell survival rate in CD34+ MF samples, comparing with no significant changes in single agent magrolimab. However, the combination of Ruxolitinib and Magrolimab significantly increases CALR membrane expression comparing with Ruxo or Magrolimab alone, signalling a much stronger pro-phagocytic message in MF cells comparing with controls. The induced CALR over-expression, could stimulate a stronger immune response in vivo, where the presence of macrophages would allow removal of CALR rich cells and potentiate the cytoreductive activity towards MF clone. These data support the rational of combining Ruxolitinib with Magrolimab in the next clinical trial stage in myelofibrosis.
Pirtobrutinib in covalent BTK-inhibitor (cBTKi) pre-treated mantle cell lymphoma (MCL): Updated results and subgroup analysis from the phase 1/2 BRUIN study with >3 years follow-up from start of enrollment.
Authors: Shah Nirav Niranjan , Jurczak Wojciech , Zinzani Pier Luigi , Eyre Toby A. , Cheah Chan , Ujjani Chaitra Shankar , Izutsu Koji , Ma Shuo , Flinn Ian W. , Alencar Alvaro Jose , Lewis David John , Patel Krish , Maddocks Kami J. , Wang Yucai , Munir Talha , Zelenetz Andrew David , Balbas Minna , Tsai Donald E , Wang Chunxiao , Wang Michael
Published: June 2023

7514

Background: Pirtobrutinib is a highly selective, non-covalent (reversible) BTKi. Here, we report updated results of pirtobrutinib in patients (pts) with cBTKi pre-treated relapsed/refractory (R/R) MCL and more than 3 years follow-up from start of enrollment. Methods: Pts with cBTKi pre-treated R/R MCL received pirtobrutinib monotherapy in a multicenter phase 1/2 BRUIN trial (NCT03740529). Efficacy was assessed in the prespecified primary efficacy cohort that comprised the first 90 enrolled pts who had measurable disease, had received a prior cBTKi, and had no known central nervous system involvement. The primary endpoint was overall response rate (ORR) as assessed by independent review committee. Secondary endpoints included duration of response (DOR) and safety. A data cut of 29 July 2022 was utilized. Results: Among MCL pts who received a prior cBTKi (n=90), median age was 70 years (range, 46-87), median prior lines of therapy were 3 (range, 1-8), 82% discontinued a prior cBTKi due to disease progression, and 78% had intermediate/high risk sMIPI score. Of samples available, 17/36 (47%) had TP53 mutations and 25/34 (74%) had Ki67 ≥30%. The ORR was 57% (95% CI, 46-67), including 19% complete responses (n=17) and 38% partial responses (n=34). At a median follow-up time of 13 months, the median DOR among the 51 responding pts was 17.6 months (95% CI, 7.3-27.2). The 12- and 18-month estimated DOR rates were 58% (95% CI, 41-72) and 45% (95% CI, 27-61), respectively. ORR and DOR by subgroups are shown in the Table. The median progression-free survival was 7.4 months (95% CI, 5.3–13.3). The median overall survival was 23.5 months (95% CI, 15.9-NE). In the MCL safety cohort (n=166), the most frequent treatment-emergent adverse events (TEAE) were fatigue (31%), diarrhea (22%), and anemia (17%). The most common Grade ≥3 TEAE was neutropenia (15%). Grade ≥3 TEAE of hemorrhage (3%) and atrial fibrillation/flutter (2%) were infrequent. Only 5 (3%) pts discontinued due to a treatment-related AE. Conclusions: Pirtobrutinib continues to show durable efficacy and a favorable safety profile in heavily pre-treated R/R MCL pts with prior cBTKi therapy. Responses were observed in pts with high-risk disease features including pts with blastoid/pleomorphic variants, elevated Ki67 index, and TP53 mutations. Clinical trial information: NCT03740529 . [Table: see text]
Impact of imaging frequency on progression free survival in Alliance clinical trials enrolling patients with untreated follicular lymphoma.
Authors: Rutherford Sarah C. , Yin Jun , Pederson Levi D , Blum Kristie A. , Martin Peter , Jung Sin-Ho , Grant Barbara , Rosenbaum Cara , Cheson Bruce D. , Bartlett Nancy L. , Mandrekar Sumithra J. , Leonard John Paul
Published: June 2023

7520

Background: With goal of simplifying clinical trials in lymphomas, we reported that bone marrow biopsies are irrelevant for response assessment in most patients (pts) with follicular lymphoma (FL) on trials (Rutherford JCO 2023). We then investigated impact of imaging frequency in FL clinical trials. We hypothesized that progression free survival (PFS) would not be different when imaging is performed less frequently than required by trials. Methods: We identified all trials through Alliance for Clinical Trials in Oncology that enrolled untreated pts with FL from 2008-2016. We considered 2 imaging schedules: protocol specified (control) vs relaxed (X) in which response assessments at every other required time point were omitted. For each trial, we estimated PFS using Kaplan Meier methods for the 2 schedules then determined difference in PFS between schedules as % change from control schedule in 2 year (yr) PFS rate. We performed simulation studies to approximate impact of less frequent imaging on PFS estimation using 50901 (low-intermediate risk FL) and 50904 (intermediate-high risk FL, control arm). We assumed exponential distribution for PFS, where rate parameter was calculated based on observed median PFS with uniform censoring distribution. Protocols for 50901 and 50904 mandated imaging every 4 months (mos) for 2 yrs then every 6 mos (S0). We ran 1000 iterations of 100 observations using 3 tumor assessment follow up schedules: every 6 mos for 2 yrs then yearly (S1), every 8 mos for 2 yrs then yearly (S2), or yearly (S3) for simulated progression times. We calculated deviation of PFS using simulated schedules from truth (S0). Results: Across 5 FL trials, median percent change of schedule X from control schedule in estimated 2yr PFS was 2.1% (0.0-30.8%) and in estimated 4yr PFS was 0.9% (-8.6-25.7%). Disparate result in 50901 is due to small shift in events with low number of pts at risk for progression. Simulation study results by trial were: for 50901, true median PFS 1.9 yrs and average median PFS for S1, S2, and S3 of 2.05, 2.11, and 2.21 yrs; for 50904 (control arm), true median PFS 4.1 yrs and average median PFS for S1, S2, and S3 of 4.16, 4.12, and 4.05 yrs. Conclusions: Our findings support decreased frequency of imaging studies in FL clinical trials, which would improve resource use and decrease pt burden. We plan a larger analysis to confirm results. https://acknowledgments.alliancefound.org . Clinical trial information: NCT00553501 , NCT01145495 , NCT01190449 , NCT01286272 , NCT01829568 .[Table: see text]
Effectiveness and safety outcomes in patients with EBV+ PTLD treated with allogeneic EBV-specific T-cell immunotherapy (tabelecleucel) under an expanded access program (EAP) in Europe.
Authors: Choquet Sylvain , Clark Andrew , Renard Cécile , Uttenthal Ben , Chaganti Sridhar , Trappe Ralf Ulrich , Comoli Patrizia , Duan Xinyuan , Xing Baodong , Wu Charley , Gamelin Laurence , Terwey Jan-Henrik , Friedetzky Anke , Dierickx Daan
Published: June 2023

7521

Background: Pts with relapsed or refractory (r/r) EBV+ post-transplant lymphoproliferative disease (PTLD) in Europe have had historically poor overall response rates and median overall survival (OS) with no approved treatment options. Tabelecleucel, an off-the-shelf, allogeneic EBV-specific T-cell immunotherapy has shown clinical benefit and favorable safety profile in the treatment of EBV+ PTLD failing rituximab ± chemotherapy (Prockop EBMT 2021, ATC 2021, ASH 2022). Its recent European marketing authorization (EMA) represents the first approval of an allogenic T-cell immunotherapy globally. Methods: Atara Bio supported expanded access requests for tabelecleucel in Europe. Here we report updated effectiveness and safety data for r/r EBV+ PTLD pts who provided consent for research between Sep 2020 and Dec 2022. Results: 74 EAP requests were received from 10 countries for pts with r/r EBV+ diseases. 27 EBV+ PTLD pts consented to secondary use of data and 24 pts had received ≥1 dose of tabelecleucel, including 4 pts with primary central nervous system (PCNS) PTLD. 16 of 24 (66.7%) PTLD pts achieved a partial (PR) (33.3%) or complete (CR) (33.3%) response, with median time to response (TTR) of 1.0 mo (0.8–2.2). Response rate for PCNS PTLD pts was 75% (1 CR, 2 PR). 1-yr OS Kaplan–Meier (KM) estimate rates were 73.7% (95% CI: 47.3, 88.3) overall, 87.5% in allogeneic hematopoietic stem cell transplant (HCT) and 66.5% in solid organ transplant (SOT), with a median follow-up time of 9.9 (2.4–13.9) and 6.0 (0.7–18.0) mo, respectively. Serious treatment-emergent adverse events (TESAEs) were reported in 7 (29.2%) pts, including 1 fatal event of disease progression. Predefined risks for tabelecleucel were reported in 3 pts; 1 (4.2%) SOT pt had a TESAE of liver transplant rejection (grade 2) and 2 (8.3%) HCT pts had non-serious TEAEs of chronic graft-versus-host disease (grade 1 and 2). No cases of cytokine release syndrome or tumor flare reaction were reported. No AEs were reported as related to tabelecleucel by the treating physician. Conclusions: These updated real-world results for pts with r/r EBV+ PTLD post-HCT or post-SOT treated in the European EAP continue to reinforce the favorable risk:benefit profile of tabelecleucel and are in line with clinical study data supporting its recent EMA approval. [Table: see text]