bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing the time toxicity of cancer treatments in the CCTG LY.12 trial.
Authors: Gupta Arjun , Hay Annette E. , Crump Michael , Djurfeldt Marina , Zhu Liting , Cheung Matthew , Shepherd Lois E. , Chen Bingshu E. , Booth Christopher M.
Published: June 2023

12135

Background: When different cancer treatments have similar oncologic outcomes, their respective time-related burdens can aid patient-oncologist decision-making regarding which treatment approach to pursue. We have previously developed a pragmatic and patient-centered metric of these time burdens-- which we term ‘’time toxicity’’-- as any day with physical healthcare system contact. This includes outpatient (e.g., bloodwork, scans, clinician, etc.) and emergency room visits, and overnight stays in a healthcare facility. Herein we sought to assess time toxicity in a completed RCT. Methods: We conducted a secondary analysis of the Canadian Cancer Trials Group LY.12 RCT that evaluated 2-3 outpatient cycles of gemcitabine, dexamethasone, and cisplatin (GDP) vs. dexamethasone, cytarabine, and cisplatin (DHAP) in 619 patients with relapsed/refractory lymphoma prior to stem cell transplant. Primary analyses reported similar response rates, transplantation rates, event-free-survival, and overall survival across arms. We calculated patient-level time toxicity by analyzing RCT forms. The study period was the date of assignment to the date of progression or the day before stem cell transplant. We considered days without healthcare contact as ‘’home days’’. We compared time measures across arms. Results: The median study duration was longer in the GDP arm (50, vs. 47 days in the DHAP arms, p=0.007). Median time toxic days were comparable in both arms (18 vs 19 days, p=0.79), but median home days were higher in the GDP arm (33 vs 28 days, p<0.001). The proportion of time toxic days (time toxic days divided by study duration) was lower in the GDP arm (34%, vs. 38%, p=0.009). The GDP arm experienced more time toxicity related to planned outpatient chemotherapy (median, 10 vs. 8 days), but the DHAP arm experienced many more hospitalization days (median, 11 vs. 0 days) (Table). Conclusions: This study demonstrates that measures of time toxicity can be extracted from RCTs. These measures can add clinical insight into patient burdens. In LY.12, despite broadly comparable short- and long-term oncologic outcomes, the GDP arm experienced less time toxicity. Such information can guide decision-making for patients with aggressive hematological cancers, who already spend a significant portion of time with healthcare contact. Clinical trial information: NCT00078949 . [Table: see text]
Prior authorizations for oral anticancer drugs and delayed prescription fills.
Authors: Kyle Michael Anne , Keating Nancy Lynn
Published: June 2023

1504

Background: Oral anticancer drugs have proliferated in recent decades. These drugs are increasingly approved based on provisional data via the FDA’s accelerated approval pathway and have high prices, motivating payers to closely monitor how they are used. We assessed use of prior authorization (PA) of oral cancer drugs for Medicare Part D beneficiaries and assessed the impact of PA on delays in prescription fills. Methods: Using Medicare Part D formulary and claims data from 2010-2019, we described trends in Part D plans’ use of PA for oral oncology drugs, identified using the Oncology Care Model drug list (excluding hormonal therapies). We then examined changes in access to imatinib after the introduction of a new PA. We focused on imatinib because it is a highly effective first-in-class drug with a generic entrant in 2016. We compared Part D beneficiaries continuously enrolled in a plan with a policy change (new PA introduced) or a control plan (no change) in the 120 days before and after the policy change or equivalent date (control) and had at least three 30-day imatinib fills in the pre period. This restriction aimed to identify individuals filling regularly and plausibly expected to continue the drug. For each index fill in the post period, we calculated predicted fill (date of previous fill + days supply received). Our outcome variable was the difference (in days) between predicted and observed index fill date, censored at 120 days for post-period observations without an observed fill. We used an event study to model predicted vs. actual time to first fill following a policy change (new PA) relative to the controls (no change), adjusting for patient age, sex, low-income subsidy, average number of days between pre-period fills, year of fill, and plan type (standalone or Medicare Advantage). Results: The proportion of oral anticancer drugs requiring a PA increased from 52.8 to 96.3% from 2010 to 2019. For imatinib, PA increased from 65% to 89% from 2010-16, the year generic imatinib entered. PA for generic imatinib was 95% on market entry. In the imatinib event study sample, there were 1,354 index fills for patients. Unadjusted mean delay in index fill was 40 days for new PA and 15 days for controls; median difference was 4 and 3 days, respectively. Discontinuation was comparable: 9.3% (new PA) vs. 9.5% (control). The adjusted difference between predicted and actual fills for new PA was 20.3 days (95% CI 6.5-34.2, p<0.004). Conclusions: Use of PA for oral oncology drugs has increased substantially over 10 years. In the setting of high prices and provisional outcomes data, PA may be appropriate. However, PA may delay fills, even for high-value drugs like imatinib. Oral anticancer drug adherence is an NCI priority; further study is warranted to identify opportunities to reduce administrative burden of PA and lessen barriers in access to effective medications.
State mandatory paid medical leave policies and survival among adults with cancer in the US.
Authors: Barnes Justin Michael , Chino Fumiko , Johnson Kimberly J. , Zheng Zhiyuan , Han Xuesong , Yabroff Robin , Johnston Kenton J
Published: June 2023

1511

Background: Cancer treatment is often costly and time intensive. Paid medical leave can help employed patients with cancer more effectively manage side effects and complete recommended cancer treatments without loss of income. Since 2012, several states have introduced mandatory paid medical leave policies. We examined whether mandatory paid medical leave policies were associated with better survival among working age adults with cancer. Methods: Adults ages 18 to 64 years diagnosed with cancer 2007- 2019 were identified from the Surveillance, Epidemiology, and End Results registry program covering 12 states. The primary outcome was overall survival (OS). The exposure of interest was the presence of state mandatory paid medical leave policies. Difference-in-differences (DID) analyses with additive hazards regression models compared changes in OS from pre- to post- mandatory paid sick leave policy implementation in states with vs. without paid sick leave policies. Models adjusted for year-quarter fixed effects, state fixed effects, state Medicaid expansion status, age, race, sex, marital status, metropolitan residence status, county-level income, cancer site, cancer stage, and insurance status. Clustered standard errors by state were achieved via the cluster bootstrap. The plausibility of the common trends assumption was tested using event study analyses and was satisfied for all analyses. Primary analyses focused on data from 2007-2016, where information on month of diagnosis, county, and insurance coverage status were available (note these variables are not available for 2017-2019), though sensitivity analyses with data through 2019 without these additional variables were conducted. Results: A total of 1,491,208 adults with cancer were identified. In adjusted DID analyses, after policy implementation, 1-year OS improved from 85.0% to 86.4% in states with mandatory medical leave policies compared to 85.1% to 85.6% in states without such policies. This translates to a 0.85% improvement in 1-year OS (hazard DID: -0.0007, 95% CI = -0.0016 to -0.0001, P = .027). The largest improvement was found among the uninsured population (hazard DID: -0.0038, 95% CI = -0.0076 to -0.0011, P = .013). In sensitivity analyses with abbreviated data through 2019, results were similar (DID for 1-year OS: 1.3%; hazard DID: -0.0010, 95% CI = -0.0025, 0.0001, P = .070). Conclusions: State mandatory paid medical leave was associated with improved survival for working-age adults with newly diagnosed cancer, particularly for those who are uninsured. Policy changes that better support patients through cancer treatment may pay off with improved cancer outcomes.
English- and Spanish-preferring patient perspectives on managing acute care needs at two disparate health systems.
Authors: Kyalwazi Beverly , Halm Ethan A , Courtney D. Mark , Sweetenham John W. , Sadeghi Navid , Cox John V. , Lee Simon Craddock , Hong Arthur
Published: June 2023

1524

Background: Although nearly every participating provider group in Medicare’s Oncology Care Model sought to reduce emergency department (ED) use by their patients with cancer, few achieved this. Despite growing spread of specialized oncology urgent care clinics (OUCC) as an ED-alternative to treat commonly anticipated treatment-related symptoms, these clinics are underused. The University of Texas Southwestern (UTSW) and Dallas County Safety-net (Parkland Health) have run OUCCs since 2015. Parkland patients use the ED twice as often as UTSW patients in the first 6 months after cancer diagnosis. Utilizing semi-structured interviews, we investigated oncology patient perspectives on acute care needs and ED decision-making in both systems among English and Spanish-preferring patients. Methods: We interviewed 24 UTSW and 16 Parkland oncology patients (5 English-preferring, 11 Spanish-preferring). UTSW is an urban regional academic referral center serving nearly 8 million people with a cancer patient population that is 35% nonwhite and 7% Medicaid or uninsured. Parkland serves patients in Dallas County including a cancer patient population that is 77% nonwhite and 80% with Medicaid or county charity care (uninsured). Translated transcripts were analyzed using iterative thematic analysis and the constant comparative method. We evaluated decision-making, attitudes, beliefs, and barriers to access that influenced decisions to present to the ED across a diverse patient population. Results: Patients in both health systems endorsed that they did not receive adequate information about expected side effects from cancer treatment. UTSW patients described direct access (e.g., personal cell phone numbers) to their oncologist, whereas Parkland patients commonly relied on non-clinician family to triage symptoms. Parkland patients reported experiencing barriers to outpatient care (lack of insurance, language barriers, and limited access to outpatient care), and described an acculturation to visiting the ED for acute care needs. When patients called a clinician for triage advice, they were often referred to the ED. Overall, patients were largely unaware of OUCCs and a 24/7 telephone triage line, but were very interested in accessing the OUCC to avoid prolonged wait times and exposure to infectious pathogens in the ED. Conclusions: Among ED-visiting patients with cancer, we found notable disparities in rapid informal access to clinicians between oncology patients receiving care through UTSW compared to Parkland. Highlighting the available 24/7 phone line as part of patient counseling on treatment side-effects might mitigate this disparity in access, increase utilization of the OUCCs, and reduce low-acuity ED visits in both health systems. Patient perspectives provide valuable insights on how to better integrate care delivery innovations for this high-risk population.
Implementation of a multi-cancer early detection (MCED) test using a centralized model within (w/i) a multi-state health system.
Authors: Agarwal Gautum , Carlson Jay W. , Broyles Damon R.
Published: June 2023

1526

Background: Cancer is the second leading cause of death globally. Currently, USPSTF recommends screening for only 5 (breast, cervical, colorectal, lung [high-risk], prostate [individualized basis]) cancers, but ~70% of cancer-related deaths are from cancers without recommended screening. Galleri (GRAIL, LLC, Menlo Park, CA), an MCED test, that uses a cell-free DNA-based targeted methylation assay and machine learning classifiers to detect a shared cancer signal and predict the cancer signal origin is available for use as a complement to existing screening tests. We present a model of centralized MCED test implementation w/i a multi-state health system. Methods: From 11/2021-7/2022, clinical and operational leadership w/i the Mercy Health System (headquartered in St. Louis, MO), including 44 acute and specialty hospitals with over 4000 integrated providers and 44000 coworkers in 5 states (MO, KS, AR, OK, IL), created an MCED test implementation plan for their health system. Results: A model with centralized navigation was developed such that patients (pts) and providers contacted a singular team (MCED team) w/i the Mercy Precision Medicine Division using telemedicine to order an MCED test and navigate processes. In the 2 months prior to and after launch (7/12/2022), 12 medical education sessions were held for various groups w/i the health system, including the centralized MCED team, leaders of subspeciality departments, and all primary care providers, to inform on the MCED test implementation plan. In this model, access to MCED testing commences in 2 ways: (1) pts register through an online form or (2) providers w/i the health system submit a referral to the MCED team through the electronic medical record system. Pts are then contacted by a nurse practitioner on the MCED team for pretest counseling w/i 2 business days. If the pt is still interested after counseling, an MCED test is ordered. Pts go to 1 of 11 Mercy labs to have their blood drawn for MCED testing. “Cancer signal detected (CSD)” test results are given to a specialized navigator who helps schedule diagnostic testing and initial appointments with specialists and coordinates follow-up care and treatment (tx) w/i the health system. Early analytics show that from launch to 1/31/2023, there were 3777 total referrals (2931 pt, 846 provider) that led to 925 MCED test orders, of which 6 had a CSD result. Median time from a CSD test result to pt notification was 22.8 hours, to initial diagnostic evaluation was 3.1 days, and to a cancer diagnosis was 8.7 days. Median time from cancer diagnosis to initiation of tx or first postdiagnosis specialist visit was 33 days. Conclusions: This model allowed for efficient time to diagnosis and tx or triage of eligible-risk pts using an MCED test and is an example of how a healthcare system can incorporate and scale the implementation of the MCED test into clinical practice.
Differential responses to systemic therapy among patients who are financially fragile and receiving Medicaid: Results from ePRO and biometric monitoring study.
Authors: Ramsey Scott David , Yu Kaiyue , Shankaran Veena , Bansal Aasthaa , Kreizenbeck Karma L. , Glascock Morgan , Watabayashi Kate , Benitez Alejandra , Wilson Richa , Yu Elaine
Published: June 2023

1527

Background: Cancer patients with Medicaid insurance have a 50% higher risk of unplanned ED admissions during systemic chemotherapy compared to commercially insured cancer patients. In a prospective study of an ePRO app and smartwatch to remotely monitor patients receiving anti-cancer therapy, we compared symptoms and biometric data among financially fragile (able vs. not to come up with $2000 in 30 days for an unexpected expense) Medicaid enrollees and commercially insured patients with solid tumor malignancies. Methods: The study was conducted at 3 community oncology practices in WA state. (ML41539, ISRCTN25569053) The ePRO had 15 common treatment-related symptoms from the PRO-CTCAE survey. 30 patients initiating systemic treatment wore a Samsung Galaxy 3 watch and completed the ePRO daily on study provided smartphones for 2 weeks. EPRO app adherence (ratio of completed to expected entries) was 91%. Smartwatch adherence (ratio of days with any biosensor data to number of days expected) was 86%. Composite symptom scores were calculated from ePRO responses using a published mapping algorithm (Range 0-3). Repeat symptoms, number of unique symptoms scores >1, and average heart rate (HR) were compared. Results: Participants’ average age was 60 (68% female; 75% no comorbidity, 45% metastatic, 10% Medicaid, 13% reported financial fragility). Treatments: chemotherapy only (56%); immunotherapy only (11%); combination therapy (33%). Financially fragile patients had significantly higher average HR, unique symptoms, and repeat symptoms (e.g., >1 day with symptoms). The average composite symptom score over 2 weeks was significantly higher for Medicaid enrollees, and trended higher for financially fragile patients. 16% of daily composite symptom scores recorded by Medicaid patients were 2 or greater, versus 7% for non-Medicaid patients (p<0.001). Conclusions: Medicaid-insured and financially fragile patients may have more adverse responses to systemic therapy compared to more advantaged patients. If supported in larger studies, the findings may have profound implications for research aimed at improving clinical management in financially disadvantaged cancer patients.[Table: see text]
Outpatient practice utilization for CAR-T and T cell engager in patients with lymphoma and multiple myeloma.
Authors: Bansal Radhika , Paludo Jonas , De Menezes Silva Corraes Andre , Megan Spychalla , Khurana Arushi , Hampel Paul Joseph , Durani Urshila , Dingli David , Hayman Suzanne R. , Kapoor Prashant , Wang Yucai , Binder Moritz , Kourelis Taxiarchis , Kumar Shaji , Warsame Rahma M. , Bennani Nabila Nora , Gertz Morie A. , Johnston Patrick B. , Ansell Stephen M. , Lin Yi
Published: June 2023

1533

Background: FDA-approved chimeric antigen receptor T-cell (CAR-T) and bispecific T cell engager (TCE) therapy are most commonly managed inpatient. Here we report our experience with hospital-based outpatient (HBO) management of patients (pts) receiving FDA-approved CAR-T or TCE and a predictive model for increased risk of early hospitalization (≤3 days post CAR-T). Methods: We reviewed the outcomes of pts who received FDA-approved CAR-T (axi-cel, brexu-cel, ide-cel, cilta-cel) or TCE (teclistamab) in the HBO unit between 3/2021 and 1/2023 at Mayo Clinic, Rochester. Results: HBO is closely integrated with inpatient practice and includes the same specialty trained clinical team. It is the first point of contact 24/7 for pts and triage evaluations. CAR-T and TCE are given on HBO followed by monitoring per REMS and as clinically needed until admission criteria is met. Remote patient monitoring (RPM) tools were used as part of outpatient monitoring. Out of 169 CAR-T pts, 87 (51%) were dosed with new indication/products (follicular lymphoma, mantle cell lymphoma, myeloma). Among those, 80 (92%) pts were dosed outpatient, among whom 21 (27%) were never hospitalized. CRS and ICANS incidences were comparable to that reported in registration studies. Median time to first admission from CAR-T infusion was 1 day (range, 0-9), with 31% (n=18/59) of admissions after day 3 post infusion. The most common cause of hospitalization was fever (n=40, 59%). Median length of hospital stay was 4 days (range, 1-49). Median time to tocilizumab (n=45, 80%), steroid (n=1, 2%), escalation of oxygen support (n=7, 12%), vasopressor (n=2, 3%), ventilator (n=1, 2%), hemodialysis (n=1, 2%) and ICU transfer (n=3, 5%) was 1 day (range, 0-31) after first admission. Use of bridging therapy, elevated CRP and LDH were predictive of early admission (ROC AUC 0.62). Four pts received teclistamab on HBO and enrolled in RPM. Data from more pts will be reported at ASCO. Conclusions: Our expanded study in CAR-T and TCE confirms that HBO is feasible and that CAR-T and TCE can be safely dosed outpatient. Approximately 31% of pts were admitted after 3 days from CAR-T infusion, and 27% of our pts were never admitted. Variables associated with aggressive disease can predict early hospitalization in pts receiving FDA-approved CAR-T. Extension of HBO practice to TCE is feasible.[Table: see text]
Overcoming barriers and improving genetic testing completion rate for hereditary cancer in an underserved population at a large safety net hospital.
Authors: Vara Autumn , Patel Tejal Amar
Published: June 2023

1538

Background: Genetic testing is a routine practice in oncology care as outcomes of germline testing may impact surgical recommendations, open therapeutic options, as well as inform patients and family members of their cancer risks. Lyndon B. Johnson Hospital (LBJ) is a safety-net hospital that mainly serves low income and uninsured patients (pts), and LBJ oncology clinic is staffed by MD Anderson Medical Oncology faculty and fellows. Pre-test counseling with a certified genetic counselor was offered once a week by referral and transitioned to virtual template at the start of the COVID-19 pandemic. This transition in addition to barriers unique to the underserved population led to a decrease in test completion rates and introduced a backlog as patients were re-referred for completion of testing. We discuss our strategies in decreasing a 9-month backlog over the course of one year. Methods: Re-introduction of an on-site general oncology genetic counselor twice a week was implemented in addition to maintaining the virtual platform once a week. The on-site genetic counselor was embedded in the physician’s clinic and rotated to ensure coverage for all clinic days. Manual chart review was conducted by on-site genetic counselor and patients were rescheduled to in-person template in conjunction with other same day appointments to improve no-show rate. Patients electing to proceed with germline testing signed appropriate written consent, patient assistance financial forms, and submitted samples prior to leaving clinic. Results: From January 2019 through December 2022, a total of 1716 patients including re-referrals were scheduled and 728 patients seen. When genetic counseling service was available as referral outside of oncology clinic, the completed visit rate was 48%, which decreased to 26% in 2020 after COVID- 19 transition to virtual. The visit completion rate did improve to 36% in 2021 but the most improvement was seen with genetic counselor embedded in physician clinic with 69% in 2022. The number of genetic testing also increased with 79 ordered in 2021 to 211 ordered in 2022. Of those patients who met national criteria for germline testing and expressed verbal consent, 47% completed germline testing in 2021 which improved to 83% in 2022. Conclusions: In our experience, telehealth genetic services is not ideal in the underserved population as there are unique barriers. On-site embedded genetic counseling helps eliminate barriers by allowing patients to complete all steps necessary prior to leaving clinic, leading to successful test completion rates and improved quality of care.[Table: see text]
Antineoplastic and immunomodulating agent effects on immunization outcomes.
Authors: New Jacob , Cham Jason , Puglisi Leah , Smith Lana , Hong Lee , Fielding Russel , Kurian Sunil , Pandey Amitabh , Nicholson Laura
Published: June 2023

1539

Background: Oncologists face a challenge in advising patients on the infection risk associated with antineoplastic and immunomodulating medications, as the extent of risk posed by each medication is not well understood. The rapid administration of COVID-19 immunizations across the population provides an opportunity to assess the influence of immunosuppressing medications on infection outcomes post-vaccination. This study evaluated the effect of antineoplastic and immunomodulating medications as classified by the World Health Organization Anatomical Therapeutic Chemical Classification System (WHO ATC) on post-vaccination risk of COVID-19 infection and antibody response to multiple SARS-CoV-2 epitopes using serial serologic assessments. Methods: At a large, tertiary healthcare system in San Diego, we conducted an observational cohort study from December 11, 2020, to September 22, 2022, comparing vaccinated adult patients taking WHO ATC-classified immunosuppressing medications (“immunosuppressed” group) with matched control patients not prescribed these medications (“immunocompetent” group) for the outcome of PCR+ COVID-19 infection. A subset of immunosuppressed and immunocompetent individuals was consented to provide serial assessments of antibody response to multiple SARS-CoV-2 epitopes using the Genalyte serologic platform. Results: 12,709 vaccinated immunosuppressed patients and 197,151 immunocompetent controls were identified for matched analysis. Receiving an immunosuppressing medication conferred increased risk of COVID-19 infection post-immunization (HR: 1.5, 95% CI: 1.38 – 1.63, p < 0.0001). Among immunosuppressing medications, PD1/PD-L1 inhibiting monoclonal antibodies and calcineurin inhibitors were associated with increased risk of COVID-19 infection (HR: 2.33, 95% CI: 1.35 – 4.04, p = 0.0038; HR 2.72, 95% CI: 1.78 – 4.16, respectively). Receiving three and four COVID-19 immunizations reduced this risk, except in patients taking calcineurin inhibitors. Among 87 consented participants, 218 samples from multiple timepoints revealed a decreased antibody response to both spike S1 and S2 subunits following third and fourth immunization. Despite decreased seroconversion, this study found medications like CD20 inhibiting monoclonal antibodies and folic acid analogs did not increase the post-immunization risk of COVID-19. Conclusions: These results help elucidate the relationship between antineoplastic and immunomodulating medications and COVID-19 immunization outcomes. In our patients, seroconversion efficacy did not always correspond to post-immunization infection, consistent with COVID-19 disease risk being multifactorial. The findings of this study inform oncologists’ shared decision-making process in advising patients of the risk of infection associated with immunomodulating medications and the potential impact on their vaccination response.
Distribution of alternate site infusion providers in the US.
Authors: Revol Cindy , Patton Catherine , Jain Sanjula , Oakes Allison H
Published: June 2023

1542

Background: Spurred by the pandemic, chemotherapy treatments provided by alternate site infusion providers have been increasing. This diversification has the potential to increase access to care and improve patient satisfaction. However, it is currently unknown how equitably distributed these non-traditional infusion settings are, and whether these newer entrants are entering markets with need or markets with ample supply. In addition, many community oncologists are concerned about the ability to retain control over a patient’s treatment and preserve the profits earned from drug infusions. Further, there are concerns regarding the lack of robust data on the safety of alternate site chemotherapy infusions. Industry analysts anticipate steady expansion in US markets for alternate site infusion with chemotherapy being a strong driver of growth. The objective of this study was to examine the distribution of alternate site infusion services across the US. Methods: Leveraging the Medicare home health infusion (MHHI) provider database from CMS, we calculated the rate of MHHI providers per 1000 Medicare beneficiaries in each US state. We reviewed company information to determine the geographic footprint of 3 alternate site infusion providers. Results: The median MHHI rate was 0.013 per 1000 beneficiaries (CO), the average rate was 0.031, with a minimum of 0 (ND, SD, WY) and a maximum of 0.202 (IL). ND, SD, WY, IN, KY, and OK have the lowest concentration of MHHI providers, whereas OR, KS, WA, NE, CA, and IL have the highest concentration. 3 alternate site infusion providers are Option Care, UnitedHealth’s Optum Infusion Pharmacy, and Coram, CVS Specialty Infusion Services. Option Care has 162 in-person infusion centers located in 45 states. Option Care’s presence is highest in CA (24), FL (9), WA (9), OH (8), VA (8), and TX (7). UnitedHealth’s Optum Infusion Pharmacy has 30 in-person infusion suites located in 20 states, primarily concentrated in FL (6) and CA (4), but also provides home infusions in all 50 states. Like MHHI providers, neither of these alternate-site providers have locations in ND, SD, or WY. Coram announced a pilot with Cancer Treatment Centers of America in 2021 to provide home chemotherapy to patients in GA, but it is unclear if that pilot is ongoing; Coram provides home infusion therapy in 49 states. Conclusions: MHHI and alternate site infusion providers are in markets across the US. If alternate site chemotherapy infusion continues to grow, health system-owned and 3rd party entrant alternate site infusion providers are likely to prosper. Conversely, physician-owned practices could face competition and loss of important drug infusion revenue leading to increased consolidation among independent oncology providers. More research is needed to determine the impact on cost and patient outcomes of alternate site chemotherapy infusions – insights that will impact reimbursement and the rate at which these services continue to grow.
Evolving adjuvant estrogen therapy prescribing among breast oncology workforce.
Authors: Polcari Kayla , Keegan Grace , Sharpe Sarah , Hahn Olwen Mary , Lindau Stacy Tessler , Skolarus Ted , Modi Parth K. , Shubeck Sarah
Published: June 2023

1546

Background: An oncologist shortage and rising number of breast cancer survivors has created a strained workforce. Care models that incorporate advanced practice providers (APPs) are recommended to meet this rising demand, particularly during survivorship. The objective of this study is to describe the evolving oncology workforce using anti-estrogen prescribing as a surrogate for breast cancer survivorship care. Methods: We used Medicare Part D Public Use Files to identify prescribers of anti-estrogen therapy from 2013 to 2020. We included medications primarily prescribed in the adjuvant setting for estrogen receptor positive breast cancer, including anastrozole, letrozole, exemestane, tamoxifen, raloxifene, fulvestrant, and toremifene. We assessed the volume of physician and APP prescribers and claims by provider type using descriptive statistics and logistic regression. Individual prescribers were included if they had more than 10 claims. Results: The overall number of anti-estrogen claims did not change significantly from 2013 to 2020, with an average of 3,224,361 annually. There was a significant increase in APP prescribers from 7,815 (8.6%) in 2013 to 12,961 (18.3%) in 2020. There was a reduction in physician prescribers by 24,815 (9.7%) over the same period with an overall net decrease of total prescribers of 19,669 (21.7%). The average annual claims per individual prescriber rose from 2013 to 2020 (Physicians: 2013: 37.5 to 2020: 45.2, p < 0.001; APP: 2013: 28.2 to 2020: 37.0, p < 0.001). The percentage of claims attributed to APP prescribers rose substantially from 6.6% in 2013 to 15.5% in 2020. This represents an increase from 220,000 prescriptions in 2013 to over 480,000 in 2020. Conclusions: Our results indicate an ongoing shift in the provider composition responsible for delivering breast cancer survivorship care. Over the time frame analyzed, there was no significant change in number of prescription claims annually, but an overall decrease in providers. Thus, the rise in APP prescribers is not driven by an increased prescribing volume, but rather seems to reflect an evolving surgical oncology workforce. This has significant implications for the future access to and delivery of timely high-quality cancer care.[Table: see text]
Prediction of cancer treatment response from histopathology images through imputed transcriptomics.
Authors: Hoang Danh-Tai , Dinstag Gal , Hermida Leandro C. , Ben-Zvi Doreen , Stossel Chani , Patil Tejas , Sammut Stephen-John , Lassoued Wiem , Allen Clint , Beker Tuvik , Jiang Peng , Golan Talia , Sowalsky Adam G. , Pine Sharon R , Caldas Carlos , Gulley James L. , Aldape Kenneth D. , Aharonov Ranit , Stone Eric , Ruppin Eytan
Published: June 2023

1551

Background: In recent years, the use of tumour molecular profiling within the clinic has allowed for more accurate cancer diagnostics, as well as the delivery of precision oncology. Rapid advances in digital histopathology have allowed the extraction of clinically relevant information embedded in tumor slides by applying machine learning methods, capitalizing on recent advancements in image analysis via deep learning. However, as in many supervised learning approaches, predicting response to therapy using whole slide images (WSI) of tissue stained with hematoxylin and eosin (H&E) requires large datasets comprising matched imaging and response data, severely restricting the applicability of this approach. Methods: To overcome this critical challenge, we introduce here for the first time a generic methodology for generating WSI-based predictors of patients’ response for a broad range of cancer types and therapies, which does not require matched WSI and response data for training. The approach, termed ENLIGHT-DeepPT, consists of: (1) DeepPT, a new deep-learning framework that predicts exome-wide tumor mRNA expression from slides, and (2) ENLIGHT, a recently published response prediction algorithm, applied here to predict response based on the DeepPT predicted expression values, instead of measured values. Results: First, we study the ability to predict tumor expression, showing that DeepPT successfully predicts transcriptomics in all 16 TCGA cohorts tested and generalizes well to two independent datasets. Second, aligned with our key aim, we analyze six independent clinical trial datasets of patients with different cancer types that were treated with various targeted and immune therapies, on which DeepPT was never trained. We show that ENLIGHT, without any adaptation, can successfully predict the true responders from the expression values imputed by DeepPT, using only H&E images: ENLIGHT-DeepPT successfully predicts true responders in these cohorts with an overall odds ratio of 2.19, increasing the baseline response rate by 38.8% on average among predicted responders. Conclusions: ENLIGHT-DeepPT is the first approach to successfully predict response to multiple targeted and immune cancer therapies directly from H&E slides, without requiring any drug-specific training data. ENLIGHT-DeepPT can provide rapid treatment recommendations without requiring tumor sequencing, bringing precision oncology to low-income countries and other situations where NGS is prohibitive.
Relevance and accuracy of ChatGPT-generated NGS reports with treatment recommendations for oncogene-driven NSCLC.
Authors: Hamilton Zac , Naffakh Noor , Reizine Natalie Marie , Weinberg Frank , Jain Shikha , Gadi Vijayakrishna K. , Bun Christopher , Nguyen Ryan Huu-Tuan
Published: June 2023

1555

Background: Next-generation sequencing (NGS) is a routine clinical practice in advanced NSCLC. NGS reports are information-dense and clinical interpretation remains a challenge. ChatGPT is a large language model (LLM) AI chatbot that can generate text in response to user-generated prompts. We sought to assess the clinical relevance and accuracy of ChatGPT-generated NGS reports with first-line (1L) treatment recommendations for NSCLC patients with targetable driver oncogenes. Methods: Eight driver oncogenes with FDA-approved targeted treatment for 1L stage IV NSCLC were identified in the latest NCCN Clinical Practice Guidelines available to the AI model (version 5, September 2021). The prompt, “Create a next-generation sequencing report with a list of first-line treatment options for a patient with stage IV non-small cell lung cancer with an [oncogenic driver].” was run in a separate “new chat” 10 times for each driver oncogene (n=80). Each ChatGPT output was recorded and scored. The Relevance Score (RS) awarded 1 point for every NCCN preferred option and 0.5 points for each “other recommended” treatment listed in the AI-generated output, divided by the maximum possible score for the driver oncogene. Spurious recommendations were awarded 0 points. The Accuracy Score (AS) represents reported treatment options listed in NCCN over the total number of treatments in a report. Percentage of reports listing an NCCN-preferred 1L therapy, a clinical trial as an option, and character and word count were also captured. Results: The average length of the AI-generated NGS reports was 117 words (range: 44 – 232). The median number of treatments recommended was 5 (range: 3 – 8). An oncogenic driver-specific preferred 1L treatment was included in 55 reports (68.8%), and a recommendation to explore clinical trials was listed in 43 reports (53.8%). The RS for the total sample was 0.59 (95% CI: 0.52 – 0.65), and the AS was 46.0% (95% CI: 40.2% – 51.8%). Conclusions: ChatGPT can rapidly generate concise NGS reports with treatment options for NSCLC with driver oncogenes. Recommendation relevance was moderate, and accuracy was limited with high variability across oncogenes. Overall, ChatGPT recommendations were promising given the complexity of the task with no prompting or training provided to the AI. As LLM AI platforms mature, they may generate more relevant and accurate NGS reports, offering a potentially valuable tool for NGS report annotation for clinicians, and increased accessibility for patients.[Table: see text]
Trial eligibility criteria (EC) and diversity among patients with advanced non small cell lung cancer (advNSCLC).
Authors: Kaur Maneet , Frahm Filip , Ascha Mustafa , Guadamuz Jenny , Gottesman Adam , Leybovich Barry , Sondhi Arjun , Zhao Yihua , Meropol Neal J. , Royce Trevor Joseph
Published: June 2023

1566

Background: FDA guidance encourages using real world data in developing diversity plans for clinical trials. Diversity plans may incorporate more inclusive (or expanded) EC, which may increase enrollment of minoritized populations. Whether broadened EC affect the diversity of eligible participants is unknown. Methods: Using the nationwide Flatiron Health electronic health record-derived deidentified database, we included patients with advNSCLC from 1/1/17-11/30/22 with a line of therapy (LOT) (N=61596). EC were defined by FDA, NCI/CTEP, and ASCO/FoCR standards, and included ECOG, ALT, AST, ALP, bilirubin, eGFR, CrCl, HGB, ANC & PLT -90 to +7 days from first LOT. Claims-linkage identified brain mets (BM), congestive heart failure (CHF), hepatitis C (HCV) & B (HBV), HIV and myocardial infarction (MI) within 6 months of first LOT. Logistic regression estimated odds ratios (OR) for exclusion by criterion associated with gender, age, race/ethnicity and area-level socioeconomic status (SES). Adjusting for clinical characteristics, Cox regression estimated hazard ratios (HR) for real world overall survival (rwOS). Results: Female patients (vs male patients) had greater odds of exclusion by CrCl (OR 2.9), eGFR (OR 1.27) & BM (OR 1.30). Compared to non-Latinx (NL) White patients, NL Black patients had greater odds of exclusion by ECOG (OR 1.17), CrCl (OR 1.33), eGFR (OR 1.61), HGB (OR 2.2), ANC (OR 1.71), HIV (OR 5.31), CHF (OR 1.31), HBV (OR 2.29) and HCV (OR 2.73); NL Asian patients by ALT (OR 1.64), ALP (OR 1.71), CrCl (OR 1.63), BM (OR 1.45) and HBV (OR 26.2); and Latinx patients by ALP (OR 1.56), HIV (OR 2.23) and HCV (OR 1.47). Compared to younger patients (18-49), older patients (75-84) had greater odds of exclusion by ECOG (OR 2.12), bilirubin (OR 1.53), CrCl (OR 41.9), eGFR (OR 9.54), CHF (OR 4.9) and MI (OR 4.7). Patients with the lowest (vs highest) quintile of SES had greater odds of exclusion by ECOG (OR 1.29) and HGB (OR 1.52). Among patients with complete data on all non-claims criteria (N=22117), the impact of expanding EC on diversity is shown, except SES which was similar. Compared to standard EC, the group with expanded EC had lower rwOS (adj HR 1.32; 95% CI 1.28-1.37). Conclusions: Expanding EC has the potential to increase the proportion and absolute number of Black, older, and female patients in advNSCLC trials. The resulting more diverse eligible population may have different clinical outcomes compared to a cohort defined by more restrictive EC. Future work will explore generalizability of findings to other clinical contexts.[Table: see text]
Toxicity reporting consistency and subjective minimizing language use in colorectal cancer (CRC) and pancreatic cancer (PaC) clinical trials: A systematic review of phase III randomized controlled trials (RCTs) presented at ASCO between 2012-2022.
Authors: Yu James , Mohammed Turab J , Chin-Yee Benjamin , Skorupski Clarissa , Gyawali Bishal , Lyman Gary H. , Adkins Lauren , Hicks Lisa K. , Kuderer Nicole M.
Published: June 2023

1567

Background: Objective and complete toxicity reporting in clinical trials is critical for patient-centered shared decision-making. Conference abstracts inform initial impressions of practice-changing treatments. Methods: We performed a systematic review of all abstracts of CRC and PaC phase 3 RCTs presented at ASCO annual meetings between 2012 – 2022; long-term follow-up, supportive care, and solely non-pharmacological studies were excluded. Objective minimization of adverse event (AE) reporting was defined as absent and/or incomplete reporting of cumulative grade 3-5 CTCAE (common terminology criteria for AE). We also assessed the use of subjective minimizing language (Chin-Yee et al ASH 2022), defined as use of “acceptable,” “tolerable”, “manageable”, “favorable” (primary minimization terms), or “feasible”, “safe”, “patients did well”, “limited” (secondary minimization terms), terms that falsely imply patients deemed the therapy as such. Presence/absence of PRO or QOL data was also assessed. Results: 63 RCTs met entry criteria (42 CRC, 21 PaC), detailed in Table. Most trials studied chemotherapy +/- other drugs (52; 83%). 17% of all abstracts did not provide any information on AE. Quantitative data on AEs were reported by 38 (60%) of abstracts. However, serious AE reporting was frequently absent (Table), with some trials reporting only specific toxicities (e.g. cytopenias) instead of cumulative CTCAE. Only 7 (11%) of abstracts noted the occurrence or absence of fatal AE. Any subjective-minimizing language was used in 15 (24%) abstracts. Notably, none of the abstracts using subjective-minimizing language provided information on fatal AE rates, nor reported on the patient perspective via QOL or PRO. Average grade ≥ 3 AE in the experimental arm were similar in abstracts with vs without minimizing language (44% vs 45%). Conclusions: Our systematic review of ph 3 RCTs in GI oncology presented at ASCO annual meetings reveals that subjective minimizing language is often used to describe serious toxicities, and without formally assessing the patient voice. Serious AE reporting is frequently absent or incomplete.[Table: see text]
Technology-enabled clinical trials: Intentional capture of source data (IDC) in the electronic-health record (EHR) and direct transfer to trial database (electronic data capture [EDC]) in a phase II multicenter trial.
Authors: Royce Trevor Joseph , Falk Sam , Xiao Forrest , Boyd Mariel , Bramwell Lindsay , Shelley Addison , Sutton Lauren , Morgan Ruth M. , Mader Patricia , Taiclet Teresa , Alve Abigail
Published: June 2023

1568

Background: Traditional data collection for clinical trials can be cumbersome and inefficient. FDA guidance now promotes capturing clinical trial source data in electronic form and transmitting it to the EDC, recognizing that this should reduce double data entry and improve data quality and timeliness. Electronic data originators can include the EHR, which can be used during routine clinical care and for gathering data during a clinical investigation. We evaluated a pilot of structured EHR data transfer to EDC in a clinical trial setting. Methods: IDC capability in the EHR was developed and applied to a subset of patients for an open label prospective Phase II study. EHR variables, that include free text, standard dictionaries (eg CTCAEv5, CDISC, First Databank), and derived responses, were mapped to the electronic case report form (eCRF). Bulk transmission of IDC clinical data (adverse events, AEs; concomitant medications, CMs; past medical history, PMH) from the EHR to EDC was executed at a designated time point during study conduct. We assessed the quantity (records) and quality (queries) of data captured and transferred, and timeliness of entry. Data to be used for the production analysis of the trial was collected via eCRF in an EDC system in parallel per usual standards. Results: Data for 102 patients across 8 sites of care by 99 different users was captured in the EHR via IDC from 3/1/2021 to 9/9/2022 and transferred from EHR to EDC in bulk on 9/9/22. 3,958 data records were transferred (852 AEs; 1,581 CMs; 1,525 PMHs). Of the AEs, 99% had an associated grade. Of the CMs and PMHs, none were copy-forwarded (all were entered de novo). Regarding queries in the EDC for transcription error validation among matching records, EHR data produced 205 opened edit check queries from 12 edit checks across all domains (149 AEs, 0 CMs, and 56 PMHs). Regarding timeliness, 95% of matched records were entered in IDC prior to entry in the production EDC. Conclusions: For an open label Phase II study, clinical trial source data was captured electronically through IDC using the EHR as the data originator, and directly bulk-transmitted to EDC. This may enable the elimination of transcription of source data entry into eCRF and result in more timely access to the data in the EDC. Additional investigation into how IDC with EHR-to-EDC compares in quality to traditional EDC is warranted. Planned follow up research includes interviewing site users to evaluate their experiences with IDC data entry.