bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world outcomes of patients (pts) with malignant solid tumors treated with immune checkpoint inhibitors (ICI) in relation to smoking status: The SAKK 80/19 SMOKER study.
Authors: El Saadany Tämer , Petrausch Ulf , Rojas Mora Alfonso , Winder Thomas , Renner Christoph , Benda Magdalena , Reimann Patrick , Froesch Patrizia , Jakob Andreas , Clavijo Daza Adriana , Müller Gisela , Von Moos Roger Anton Fredy , Mark Michael Thomas 
Published: June 2023

6619 Background: ICIs are the standard of care for the treatment of different advanced solid organ tumors. Especially in advanced non-small-cell lung cancer, never-smokers were shown to have an inferior outcome when compared to ex-smokers/smokers, suggesting that the smoking status could be a predictive marker for survival benefits under ICI treatment. Methods: Pts within the Swiss Alpine Tumor Immunology Registry (AlpineTIR) treated with an ICI were differentiated by their smoking status (ex-smokers/smokers versus never-smokers). Overall survival (OS) and progression-free survival (PFS) from the start of the first ICI treatment were analyzed by smoking status. Further, subgroup analyses for OS and PFS were done for the most common disease entities. Results: A total of 702 pts were included, from which 455 pts (65%) were ex-smokers/smokers, 213 pts (30%) were never smokers, and 34 pts (5%) had an unknown smoking status. The median follow-up time from the administration of the first ICI to the statistical analysis was 2.7 years (95% CI: 2.3 to 3.2 years). The most frequent tumors were lung cancer (50%), melanoma (13%), renal cell cancer (7%), bladder cancer (6%), and others (24%). Across all indications, the median OS was 1.7 years (95% CI: 1.4 to 2.6 years) for never-smokers (n = 213) and 1.5 years (95% CI: 1.2 to 1.8 years) for smokers (n = 455) (HR: 1.10, 95% CI: 0.89 - 1.37). The median PFS was 6.3 months (95% CI: 4.4 to 8.3 months) for non-smokers and 6.2 months (95% CI: 5.2 to 7.0 months) for smokers (HR: 1.05, 95% CI: 0.87 - 1.27). In lung cancer pts, the median OS was 1.4 years (95% CI: 0.8 to 2.8 years) for never-smokers (n = 43) and 1.4 years (95% CI: 1.2 to 1.7 years) for smokers (n = 302) (HR: 1.02, 95% CI: 0.68 - 1.51). In melanoma pts, the median OS was 3.4 years (95% CI: 1.8 to not reached (NR) years) for never-smokers (n = 54) and 1.7 years (95% CI: 0.8 to NR years) for smokers (n = 34) (HR: 1.35, 95% CI: 0.72 - 2.53). In renal cell cancer pts, the median OS was 1.5 years (95% CI: 1.0 to 3.6 years) for never-smokers (n = 28) and 3.5 years (95% CI: 0.6 to NR years) for smokers (n= 17) (HR: 0.74, 95% CI: 0.31 - 1.78). In bladder cancer pts, the median OS was 1.8 years (95% CI: 0.6 to NR years) for never-smokers (n = 17) and 1.4 years (95% CI: 0.5 to NR years) for smokers (n = 26) (HR: 0.88, 95% CI: 0.39 - 1.99). Conclusions: No survival difference between smokers and non-smokers with metastatic solid organ tumors treated with ICIs could be detected. Interestingly, even in the subgroup of lung cancer pts, no difference was seen. Based on these data, the smoking status should not guide ICI treatment decisions.
Rates of emergency department visits and acute-care hospital admissions after starting chemotherapy or having surgery across six community-based cancer centers.
Authors: Hassett Michael J. , Cronin Christine , Tramontano Angela , Wong Sandra L. , Uno Hajime , Paudel Roshan , Bian Jessica J , Dizon Don S. , Hazard-Jenkins Hannah W. , Osarogiagbon Raymond U. , Schrag Deborah 
Published: June 2023

6621 Background: Cancer patients who start chemotherapy or have surgery are at risk for serious adverse events, which can include emergency department visits (EDV) and acute-care hospital admissions (ADM). These events are relevant to patients, clinicians, health systems, and policy makers. Few studies have described the frequency and predictors of EDVs and ADMs in the routine care setting. We sought to address this knowledge gap, and to describe the impact of the COVID pandemic on these events, using data from the SIMPRO consortium of six US-based health systems. Methods: In 2019, SIMPRO started a phased deployment of an electronic health record-integrated symptom management program (eSyM) as part of the routine care provided to patients with a suspected or confirmed gastrointestinal, thoracic, and gynecologic malignancy. eSyM prompts patients to complete symptom questionnaires and provides symptom management resources for 180 days after starting chemotherapy and 60 days following surgery. This analysis includes all patients, whether they used eSyM resources or not. Outcomes, which were measured using EHR-based encounter data, included the rates of EDVs and ADMs at 30 and 90-days after starting chemotherapy or following discharge from surgery. To account for potential confounding, we used multivariable logistic regression for the 30-day outcomes and Cox regression for the 90-day outcomes. Results: From September 2019-December 2022, 8664 patients started chemotherapy and 11,578 had surgery, with 3075 and 2587 patients, respectively, experiencing at least one outcome event (Table). 90-day outcomes varied significantly across health systems for chemotherapy (EDV 2-21%, ADM 5-28%) and surgery (EDV 7-14%, ADM 9-18%) patients. In multivariable analyses, patients who reported an employment status of disabled were more likely to report an EDV (OR 1.73-1.96) and an ADM (ORs 1.52-1.96). Widowed status was associated with greater odds of having an ADM (ORs 1.29-1.30), but not an EDV. Cox regression found chemotherapy recipients experienced lower hazards of an EDV, but not an ADM, during 2020 (coinciding with the start of the COVID pandemic). For surgery patients, there was no significant association between calendar year and EDVs or ADMs. [p<0.001 for all reported values]. Conclusions: A meaningful proportion of patients who started chemotherapy or had surgery for a suspected or confirmed malignancy in the routine-care setting had an EDV or ADM within 90 days. Most events occurred within 30 days. Further work is required to ascertain how many of these encounters are avoidable and what structural or procedural interventions could improve outcomes. Clinical trial information: NCT03850912 . [Table: see text]
Efficacy-effectiveness gap with immune checkpoint inhibitors in solid cancers: A population based cohort study.
Authors: Niraula Saroj 
Published: June 2023

6625 Background: Immune checkpoint inhibitors (ICIs) have been central in oncology drug development in the last decade often demonstrating large improvements in overall survival (OS) in pivotal randomized controlled trials (RCTs). Patient selection and/or care may be less stringent in the real world but ascertaining that benefits are translated satisfactorily from pivotal RCTs into the real world is crucial, as patients often base their treatment decisions on outcomes quoted to them from pivotal RCTs. Methods: After necessary ethics approvals, we collected relevant data on all consecutive patients with advanced solid cancers treated with ICIs in the province of Manitoba, Canada from inception to June 30, 2022 using pharmacy database and cancer registry. Eight most frequent ICI indications are included here. Survival probabilities were plotted using Kaplan-Meier Method, and descriptive statistics used to report relationship between variables. To put outcomes into perspective, we report real world data alongside that of pivotal RCTs used to support approvals of respective ICIs by Health Canada and the US FDA. Results: Eight ICI indications included 992 patients followed for a median of 40 months (range: 21-86 months). Patients required to meet precise provincial formulary criteria to receive ICIs, adopted mostly from the inclusion criteria of the corresponding pivotal RCTs. Median OS was shorter in the real world population not only compared to the experimental arms of the respective pivotal RCTs [by a median of 16 months (range: 3 - 38 months)] but also compared to their control arms [by a median of 3 months (range 3 to 32 months)]. This translated into an average of 51.1% (standard deviation: 20.1) compromise in median OS with ICIs in the real world compared to that observed in respective pivotal RCTs. Conclusions: Treatment with ICIs within high standards of practice in a Canadian province overall offered less than half the median OS observed in pivotal RCTs supporting their approvals. Current ICI treatment decisions by patients (and physicians) may therefore be based on highly inaccurate expectations. Our results should inspire rigorous phase IV clinical studies to identify pertinent real-world variables affecting outcomes including treatment related morbidity and mortality, with an ultimate aim to narrow the alarming efficacy-effectiveness gap. [Table: see text]
Electronic health record (EHR)-based machine learning (ML) to predict disease recurrence after surgical resection of early-stage non-small cell lung cancer (eNSCLC).
Authors: Pisano Steven , Honarvar Hossein , Parikh Ravi Bharat , Das Rahul K 
Published: June 2023

6626 Background: Surgical resection (SR) is a guideline-recommended definitive therapy for patients (pts) with eNSCLC. However, 30–50% pts develop disease recurrence (DR) within the first 5 years (yrs) after surgery. ML applied to routinely collected EHR data could facilitate timely identification of pts at risk of DR who would benefit from enhanced surveillance or initial treatment (Tx) intensification. Methods: eNSCLC pts with stage IB-IIIA at the time of SR between Jan 2010 – February 2022 were identified from ConcertAI Patient360 oncology database comprising structured and curated records from US-based EHR. DR was defined as the human-curated earliest advanced/metastatic diagnosis date from SR. Gradient boosting (GB), random forest (RF), and logistic regression (LR) algorithms with 6-fold nested cross-validation were trained and compared to predict the risk of DR or death at 2 yrs from SR. Pts who did not experience DR and were lost to follow-up within 2 yrs from SR were removed. Feature importance was defined using Shapley Additive Explanation (SHAP)-derived odds ratios (OR). Due to low prevalence of DR at 2 yrs, AUPRC was used as performance metric. Pts in the 1st and 4th quartiles of predicted probabilities from XGB model were defined as low-risk vs. high-risk groups. Results: Among 3597 pts, median age was 68.3 yrs (IQR 12.5), 51.8% were female, and 8.6% were Black. 24.4% developed DR within 2 yrs. GB, RF, and LR models had similar ability to predict DR at 2 yrs with mean hold-out set AUPRC of 0.33. In GB model, DR prevalence at 2 yrs was 34% in the high-risk vs. 18% in the low-risk group in hold-out set. N0 stage, T stage < 3, receipt of adjuvant immune checkpoint inhibitor (ICI), and presence of EGFR mutations were protective against DR at 2 yrs, while history of anemia and congestive heart failure (CHF) were risk factors (Table). SHAP revealed a N stage-by-adjuvant therapy and a N stage-by-CHF interaction: benefit from adjuvant chemotherapy (CT) was limited to higher N stages, while adjuvant ICI was beneficial for all N stages. CHF was a risk factor for lower N stages but not for higher N stages. Conclusions: ML applied to structured and unstructuredEHRs identified predictors of risk of DR at 2 yrs after surgery in eNSCLC and may identify high-risk pts who would benefit from enhanced surveillance plans and Tx intensification in the eNSCLC setting. The model indicated favorable outcome from adjuvant targeted therapies in EGFR mutated pts. [Table: see text]
Evaluation of studies with commonly used real world data sources submitted to ASCO journals: Initial steps toward furthering transparent reporting.
Authors: Bates Benjamin , Kania Brooke , Ketelhut Ashley , Aneja Sanjay 
Published: June 2023

6630 Background: Real world data (RWD) are used to understand treatment, care, and outcomes of patients with cancer. Reporting guidelines for observational studies, such as RECORD (health), RECORD-PE (treatment) and TRIPOD (prediction), were developed to increase the transparency of studies using RWD. These guidelines are not required for publication in ASCO Journals (JCO- Journal of Clinical Oncology, PO- Precision Oncology, OP- Oncology Practice, CCI- Clinical Cancer Informatics, GO- Global Oncology). Our objective was to describe the use of RWD among studies submitted to ASCO Journals and evaluate the applicability of guidelines and adherence to guidelines. Methods: ASCO submission system was used to identify all studies submitted to ASCO Journals between 2018-2022. Based on the abstract, the studies were categorized on whether selected RWD were used: SEER, Medicare, National Cancer Database [NCDB], Flatiron, CancerLinQ, IQVIA, Optum, MarketScan. Through manual review of the published manuscripts, we calculated positive predictive value (PPV) of our algorithm to identify the RWD. We estimated acceptance rate. For each study we evaluated the following: (1) linkages with other RWD; (2) applicability of reporting guidelines RECORD, RECORD-PE, TRIPOD; (3) use of flow diagram (RECORD) or study design figure for treatment and outcome assessment (RECORD-PE). Results: The PPV of our search algorithm was 79% (95%CI 73-84) but varied by journal (PPV 73-100; p=0.02). Based on our algorithm, among the 16,133 original reports submitted, 1,156 (7.2%) used one of the RWD sources. Overall acceptance rate among RWD sources was 18%. There was variability in submissions and acceptance rate of RWD by journal. OP and GO most and least frequently received a manuscript with the selected RWD 13% and 1%, respectively. GO accepted 77% of manuscripts that used selected RWD (88% of which were SEER). JCO accepted 3.5% of RWD manuscripts. Medicare, SEER, and NCDB were frequently identified data sources (61%, 31%, and 11%, respectively). SEER was linked to Medicare claims, surveys, or other sources in 77% of studies. The other data sources accounted for <5% each, although submission of EHR-linked to claims/registry increased over time (OR 1.26: 95%CI 1.07-1.49). RECORD, RECORD-PE and TRIPOD were applicable to 100%, 10% and 8% of the studies. RECORD-PE and TRIPOD were most applicable to PO/OP/CCI and CCI, respectively. A flow diagram demonstrating selection of participants was present in 31% of the studies. A figure to visualize study design was used in <5% of RECORD-PE relevant studies. Conclusions: RWD are commonly submitted and published within ASCO Journals. Reporting guidelines are applicable and particularly important when linkages occur. Studies using oncology RWD may benefit from reporting guidelines tailored to the unique qualities of these data sources and populations.
Real world data for venous thromboembolisms (VTEs) in patients with active cancer: Thromboprophylaxis pooled analysis from GMaT and ACT4CAT studies.
Authors: Tsoukalas Nikolaos , Christopoulou Athina , Timotheadou Eleni , Koumarianou Anna , Ardavanis Alexandros , Athanasiadis Ilias , Demiri Stamatina G , Bokas Alexandros , Samelis Georgios , Peroukidis Stavros , Papatsibas George , Andreadis Charalampos , Nikolakopoulos Achilleas , Psyrri Amanda , Kapodistrias Nikolaos , Papakostas Pavlos , Aravantinos Gerasimos , Athanasiadis Athanasios , Papakotoulas Pavlos , Boukovinas Ioannis 
Published: June 2023

6637 Background: Venous Thromboembolisms (VTEs) lead to many negative consequences for patients with active cancer and are reported up to 20%. They affect anticancer treatment plan, increase morbidity, mortality, economic burden, and escalate psychological drain. Current guidelines recommend pharmacologic prophylaxis for thrombosis in ambulatory cancer patients with Khorana score ≥2. Methods: GMaT and ACT4CAT are prospective observational phase IV studies conducted by HeSMO in Greece. The aim was to record the clinical practice for ambulatory patients with active cancer who received thromboprophylaxis and enrolled after signing informed consent. Studies were approved by the bioethics committee. Results: 1157 patients from 26 oncology clinics enrolled who received thromboprophylaxis. Tumor types: gastrointestinal 38.5%, lung 24.8%, urological 12.2%, gynecological 6.9%, breast 6.1% and others 11.5%. Treatment lines: 1st 62.5%, 2nd 15.1%, 3rd 4%, adjuvant 9.7% and neoadjuvant 5.9%. Age ≥65 in 55.2%, BMI ≥30 in 17.8% and males 59.9%. High-Risk for Thrombosis Agents (HRTAs) received 82.3%: platinum agents (52.9%), antimetabolites (49.0%) and immunotherapy (10.2%). Notably, 52.7% of anticancer agents had potential drug-drug interactions (DDIs) with Direct Oral Anticoagulants (DOACs). High thrombotic risk factors presented in table. Thromboprophylaxis duration was 5.1±3.3 months with: tinzaparin 91.2%, fondaparinux 4.6%, bemiparin 2.3%, enoxaparin 1.2%, rivaroxaban 0.4% and apixaban 0.3%. Intermediate thromboprophylaxis doses of Low Molecular Weight Heparins (LMWHs) received 62% of patients; 50% in adjuvant setting & 72.6% in metastatic. 32 thrombotic events reported (efficacy: 97.2%, 95%CI: 96.3-98.2%) and 26 grade 1 or minor bleedings (2.2%, 95%CI:1.4-3.1%). Patients receiving intermediate doses of LMWHs had less risk for thrombosis (p=0.0308). Conclusions: VTEs prophylaxis in ambulatory patients with active cancer was found safe and effective. Apart from Khorana score, metastasis, HRTAs and DDIs seem to affect clinical decision for thromboprophylaxis mainly with LMWHs and often using intermediate doses irrelevant of clinical setting. Cancer Associated Thrombosis (CAT) is not negligible risk for patients and oncologists appeared to be aware about this. Clinical trial information: NCT03292107 , NCT03909399 . [Table: see text]
Cost of genetic testing, delayed care, and suboptimal treatment associated with polymerase chain reaction (PCR) versus next-generation sequencing (NGS) testing strategies in metastatic non-small cell lung cancer (mNSCLC).
Authors: Bestvina Christine M. , Waters Dexter , Morrison Laura , Emond Bruno , Lafeuille Marie-Hélène , Hilts Annalise , Lefebvre Patrick , He Andy , Vanderpoel Julie 
Published: June 2023

6638 Background: NGS testing for genomic alterations has been found to expedite time to appropriate targeted therapy initiation compared to PCR testing in mNSCLC. This study assessed US payers’ costs of testing, delayed care, and suboptimal treatment initiation for PCR versus NGS testing in patients with mNSCLC. Methods: A decision tree model evaluated testing for guideline-recommended alterations (EGFR, ALK, ROS1, BRAF, KRAS, MET, HER2, RET, NTRK1/2/3) in patients with newly-diagnosed mNSCLC from first test until appropriate therapy initiation using 1) liquid or tissue NGS (60% [90% tissue, 10% liquid] of patients), 2) exclusionary KRAS test followed by sequential PCR tests (5%), 3) sequential PCR tests (5%), or 4) hotspot panel (30%) PCR tests. The proportion of patients testing positive for a targetable alteration and time to appropriate therapy initiation were evaluated. Cost components included genetic testing, testing-related medical services, delayed care (i.e., costs for medical services while waiting for test results), immunotherapy [IO]/chemotherapy [CTX] initiation prior to test results, and suboptimal treatment initiation after test results (i.e., costs of first-line IO/CTX in patients falsely testing negative for an actionable mutation). Results: In a modeled cohort of 1 million members (75% commercial, 25% Medicare), an estimated 1,119 patients had mNSCLC and were tested. The proportion of patients testing positive for a targetable alteration was 45.9% for NGS and 39.4% for PCR testing (Table). Total mean per patient costs were lower for NGS ($8,866) than for PCR ($18,252), driven by more rapid treatment with appropriate therapy (2.1 versus 5.2 weeks), resulting in lower delayed care costs and IO/CTX costs prior to test results. Conclusions: Results suggest that NGS testing may lead to better patient care and reduced costs to the health system relative to PCR testing. Costs of inappropriate IO/CTX initiation are an important component of increased costs of PCR-based approaches. [Table: see text]
Association between targeted cancer drug net health benefit and uptake, patient out-of-pocket spending, and total spending.
Authors: Lau-Min Kelsey S. , Wu Yaxin , Rochester Shavon E. , Bekelman Justin E. , Kanter Genevieve P. , Getz Kelly D. 
Published: June 2023

6644 Background: Targeted cancer drugs (TCDs) have revolutionized oncology, but they are widely variable in their clinical benefit and are often accompanied by high patient-out-pocket (OOP) costs. The ASCO Value Framework uses published clinical trial data on survival, toxicity, and potential for symptom palliation to quantify the net health benefit (NHB) of any given cancer drug. We aimed to evaluate the association between NHB and uptake, patient OOP spending, and total spending for eight oral TCDs approved for the first line treatment of an advanced solid tumor based on one or more clinical trials comparing to a non-TCD control arm. Methods: We conducted a retrospective cohort study of incident pharmacy claims for oral TCDs prescribed to patients aged 18-64 years between 2012-2020 in the nationwide Health Care Cost Institute de-identified commercial claims dataset. NHB scores were calculated for each TCD of interest using the ASCO Value Framework and categorized as high (>60), medium (40-60), and low (<40) net health benefit. Distributions of incident 28-day TCD supplies were plotted over time by NHB category. The primary outcome was patient OOP spending (patient copay + coinsurance + deductible), whereas the secondary outcome was total spending (patient OOP spending + pharmacy reimbursement). Generalized linear models were used to evaluate the association between each outcome of interest and TCD NHB, adjusted for cancer indication. Results: We included 8,524 incident pharmacy claims for eight TCDs with nine indications in breast cancer, non-small cell lung cancer (NSCLC), melanoma, and pancreatic cancer. NHB scores ranged from 7 (erlotinib for pancreatic cancer) to 81 (crizotinib for ALK-rearranged NSCLC), with 1,145 (13%), 6,608 (78%), and 771 (9%) of pharmacy claims falling into low-, medium-, and high-NHB categories, respectively. Medium- and high-NHB TCDs accounted for the majority of incident TCD prescriptions throughout the study period. Median patient OOP spending was $18.78 for the first 28-day TCD supply (IQR $0.00-$87.57), with 45% of patients paying $0 and 8% paying >$1,000 OOP. Patient OOP spending was not significantly associated with TCD NHB category (difference $0.94, 95% CI -$49.99-$51.87 for medium vs low NHB; difference $58.86, 95% CI -$28.04-$145.75 for high vs low NHB). Median total spending was $10,118.79 (IQR $6,365.95-$10,600.37) for an incident 28-day TCD supply. There was a $1,083.56 increase in total spending for each 10-point increase in NHB score (95% CI $1,050.27-$1,116.84, p <0.01 for H0 = $0). Conclusions: Although TCDs are widely variable in their NHB, low-NHB TCDs are not prescribed as frequently as medium- and high-NHB TCDs. Total spending on TCDs is high and positively associated with NHB. Commercially insured patients are largely shielded from high OOP spending on TCDs.