bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment patterns and outcomes in resectable early stage NSCLC: Interim analysis of a global real-world study.
Authors: Lin Steven H. , Ahn Myung-Ju , Nagar Saurabh P. , Affi Raafet , Agulnik Jason , Shih Jin-Yuan , Hochmair Maximilian J. , Tufman Amanda , Debieuvre Didier , Jimenez Maria , Davis Keith , Kahangire Doreen A. , Servidio Leslie Ann , Veluswamy Rajwanth 
Published: June 2022

e18803 Background: Complete surgical resection is the preferred treatment for early stage NSCLC, with adjuvant chemotherapy as the standard of care in resected stage II/III and select stage IB NSCLC. Osimertinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), is approved as adjuvant therapy in patients (pts) with resected stage IB–IIIA EGFR mutation-positive (EGFRm) NSCLC following results from the Phase III ADAURA trial. Understanding real-world clinical outcomes in early stage NSCLC, including EGFRm prevalence, will help inform unmet needs and further development of new treatment strategies in this population. We report interim results from a global non-interventional retrospective study of pts with resectable NSCLC using clinical data from medical records. Methods: Eligible pts (aged ≥18 yrs) had completely resected stage IA–IIIA NSCLC diagnosed between Jan 1, 2014 and Dec 31, 2017 with EGFR test results available and were followed to at least Dec 31, 2020. Primary endpoints included EGFRm prevalence, treatment patterns, and overall survival (OS); disease-free survival (DFS) was an exploratory endpoint estimated by Kaplan-Meier at predefined landmark timepoints. Results: Of 463 pts from 6 countries (31% from Taiwan, 21% Canada, 17% US, 13% Austria, 10% South Korea, 9% France), median age was 66 yrs (range: 33–86); 172 pts (37%) had stage IA NSCLC at initial diagnosis and 291 (63%) had stage IB–IIIA (22% IB, 13% IIA, 10% IIB, 18% IIIA). 213/463 pts (46%) were EGFRm (43% stage IA, 61% IB, 43% IIA, 26% IIB, 47% IIIA), of who 46% were from Taiwan, 21% South Korea, 14% Austria, 8% Canada, 7% US, and 4% France. In pts with EGFRm vs EGFR wild-type (wt) NSCLC, 84/213 (39%) and 83/250 (33%), respectively, received (neo)adjuvant therapy, of who 156/167 pts (93%) had stage IB–IIIA NSCLC. 106/156 pts (68%) had disease recurrence or death from time of surgery; recurrence rates were similar in pts with EGFRm vs EGFRwt NSCLC, though median DFS was longer in the EGFRm group (Table). Recurrence rates were high in both EGFRm and EGFTwt groups, with landmark DFS probability of 72% vs 77% at 12 mo and 29% vs 32% at 60 mo, respectively. Conclusions: In this real-world global study of surgically resected stage IA–IIIA NSCLC in pts who received an EGFR test, nearly half of the study cohort were EGFRm positive, of who 70% were treated in Taiwan/South Korea. The high rate of recurrence in pts with stage IB–IIIA NSCLC despite receiving (neo)adjuvant therapy reinforces the need for early diagnosis and EGFR testing to identify pts who might benefit from EGFR-targeted therapy, helping optimize clinical outcomes.[Table: see text]
Cost-effectiveness of mt-sDNA versus mailed FIT outreach for Medicare Advantage enrollees using the CRC-AIM microsimulation model.
Authors: Bhatt Jay , Chen Jing Voon , Vahdat Vahab , Fendrick A. , Lieberman David A. , Brooks Durado , Ozbay A. Burak , Karlitz Jordan J. 
Published: June 2022

e18827 Background: Despite proven effectiveness in reducing colorectal cancer (CRC) cases, screening for CRC remains underutilized, including those enrolled in Medicare Advantage. A mailed fecal immunochemical test (FIT) outreach program may increase CRC screening adherence. This study examined the cost-effectiveness of stool-based tests (FIT and multi-target stool DNA [mt-sDNA]), with FIT offered via a mailed outreach program, in a Medicare Advantage population. Methods: The validated CRC-AIM microsimulation model was used to simulate the costs and clinical outcomes of 2 million average-risk individuals, free of diagnosed CRC at age 40, who initiated CRC screening at age 65. Annual mailed FIT outreach and triennial mt-sDNA were assessed. Test sensitivity and specificity inputs were based on the 2021 United States Preventative Services Task Force modeling study. FIT outreach program cost ($25.92) and direct costs for screening tests, colonoscopies (COLs), complications, and CRC care were included. The model employed a lifetime horizon, 3% discount rates, and a Medicare Advantage perspective. The primary analysis used published real-world adherence rates for stool-based tests and follow-up COLs (FIT/COL: 29%/53%; mt-sDNA/COL: 69.8%/71.5%). Secondary analyses assumed 100% adherence for stool-based tests and/or follow-up COLs and 20% higher than primary analysis for FIT and the corresponding follow-up COLs. Results: In the primary analysis, mt-sDNA had the greatest life-years gained (LYG), incidence reduction (IR), and mortality reduction (MR) and was cost-effective at a willingness-to-pay threshold of $50,000/QALY compared to mailed FIT outreach (Table). This was true when 100% adherence was assumed for follow-up COL and when FIT had 20% higher adherence than the primary analysis. mt-sDNA had 64-129% greater LYG, 79-150% greater IR, and 68-146% greater MR than mailed FIT outreach. When assuming 100% adherence for both screening test and follow-up COL, mt-sDNA was dominated by mailed FIT outreach. Conclusions: Adherence to CRC screening modality and follow-up COL greatly impacts clinical and cost-effectiveness outcomes. Future analysis should consider evidence-based, health plan-specific data to accurately reflect outcomes that aid in payer decision making.[Table: see text]
Novel ways to fund cost-efficiency studies of expensive drugs: Efforts to maintain sustainable healthcare expenditure in the Netherlands.
Authors: Barjesteh van Waalwijk van Doorn-Khosrovani Sahar , van der Flier Silvia , van den Berg Denise 
Published: June 2022

e18831 Background: The rising costs of new cancer drugs is a major burden for healthcare system. Healthcare providers and payers constantly look for solutions to reduce inefficient use of these drugs. Methods: These solutions may involve dose-rounding, dose-banding or vial-sharing to minimise the quantity of discarded pharmaceuticals. Alternative dosing strategies, such as tapering and/or increasing the dose-interval, shortening treatment duration, or boosting potency of the drugs may also be applied. Another approach is the development of predictive/monitoring biomarkers that can prevent mis-prescribing and overuse of therapies to patients who will not benefit from such a therapy. Provided that the therapeutic benefit is retained, a lower drug exposure evidently not only results in savings for the national healthcare budget but may also limit (off-target) toxicity, reduce hospitalisation and improve quality-of-life for patients. Results: Once compelling evidence of non-inferiority is available, the roll-out one of the strategies mentioned above is justified. Parties providing financial support for cost-efficiency initiatives are then often eager to support implementation and generate potential shared savings. However, when (additional) research is required to generate adequate evidence, fund raising and finding support can be quite challenging. In the Netherlands a dedicated national fund was recently established. Treatmeds, a foundation under Dutch law, is tasked to support cost-efficiency studies and to secure and manage (part of) the funding needed for those initiatives. Treatmeds is backed by Dutch healthcare insurers. Its governance provides for decisions based on the advice of an independent Scientific Advisory Board, an Intervention Board and a Financial Board. The Scientific Advisory Board aides with selecting studies for support on a pure scientific basis, the Intervention Board considers aspects as efficiency, the possibility of reimbursement under the Dutch compulsory healthcare insurance, the cost-benefit ratio of a study and the Financial Board ultimately decides on the financial aspects of supporting a study. Although Treatmeds only has just started its activities, it is expected that it can have a pivotal role in acceleration of efficiency tools in clinical practice. Conclusions: From our own experience we can state that a dedicated national fund supporting research on improved efficiency and quality of care can be of great value to accelerate study start-up and roll-out.
Projected impact of oncology biosimilar substitution from the perspective of provider risk in value-based oncology payment models.
Authors: Yang Jingyan , Chaudhry Basit Iqbal , Yue Andrew , Kelton John M. , Shelbaya Ahmed , Tran Lisa , Li Meng 
Published: June 2022

e18836 Background: Oncology biosimilars may play an important role in managing risk for providers participating in value-based payment (VBP) models. The impact of biosimilar substitution on risk to providers remains unclear, as prior researchers have adopted a generic budget impact approach. Methods: We estimated the impact of biosimilar substitution on financial risk to providers in oncology VBPs by applying simulation approaches to model the quantitative methodology (e.g. episode framing, pricing, risk adjustment) of Medicare’s Oncology Care Model (OCM). Patient demographic and utilization data to fit the models were drawn from the Medicare Limited Data Set (LDS). Risk was defined as total cost of care (TCOC) relative to target price for an episode per the OCM methodology. Target prices were estimated using the most recently available OCM risk adjustment coefficients (2020). Biosimilars for six oncology agents were examined: bevacizumab, rituximab, trastuzumab, epoetin alfa, filgrastim, and pegfilgrastim (hereafter biosimilar investigation agents – BIAs). Episode TCOC was computed under the assumption of the use of reference BIAs and was then recomputed after biosimilar substitution. The study population consisted of 1620 episodes framed per the OCM methodology using the most recently available LDS data (2019-2020) that had use of a BIA. The impact to provider groups was estimated by computing the change in OCM risk bands (incentive payment earned/ neutral/ payment owed back to Medicare) associated with biosimilar substitution in panels of 100 randomly selected episodes from the study population over 10000 simulation runs. In our base model, we assumed that substitution for antineoplastics would occur only in treatment naïve patients and that substitution for supportive therapies would occur for all eligible patients. Treatment naïve status was assessed by examining longitudinal LDS data from 2016-2020 for beneficiaries from the study population. Results: Biosimilar substitution resulted in a mean reduction in cost relative to target of approximately $1,200 per eligible episode and reduced the proportion of practices that were above benchmark for eligible episodes by 33% and increased the number of practices below target for eligible episodes by 42%. Additional scenario analyses suggested that adoption strategy was a major determinant of potential impact. If assumptions of antineoplastic substitution requiring treatment naïve status were relaxed, costs savings relative to target would go from $1200 per eligible episode to $2700. Conclusions: Biosimilar substitution significantly reduces aggregate provider risk in OCM, representing a significant potential intervention for providers to mitigate risk in oncology VBPs both in terms of absolute costs saved relative to target and reduction in risk band relative to payer projections.
Advanced care planning (ACP) intervention for older patient with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).
Authors: LoCastro Marissa , Sanapala Chandrika , Watson Erin , Kluger Benzi , Norton Sally , Bernacki Rachelle , Carroll Thomas , Klepin Heidi D. , Mendler Jason , Loh Kah Poh 
Published: June 2022

e19004 Background: The Serious Illness Care Program (SICP) is an evidence-based intervention that promotes ACP for patients with advanced cancer. As part of a study to adapt the SICP for older patients with AML and MDS, we identified clinician and patient reported barriers to ACP for this population, and their suggestions to improve ACP. Methods: In single-center qualitative study, we conducted semi-structured interviews with 14 oncology clinicians and 7 patients with AML or MDS. Interviews were audio-recorded and transcribed. Two investigators independently coded all transcripts using MAXQDA and resolved discrepancies through iteration. Direct content analysis techniques were used to focus on ACP barriers and suggestions. Results: Mean ages of clinicians and patients were 45 and 73, respectively. Majority of patients were not familiar with ACP. All patients had a healthcare proxy. Half of patients were familiar with a Medical Orders for Life-Sustaining Treatment (MOLST) form. Two major themes identified by clinicians and patients were: 1) Discomfort and logistics as ACP barriers (Table) and 2) ACP visit structure. Both clinicians and patients suggested the importance of earlier ACP visits. Clinicians suggested separate outpatient ACP visits, while patients suggested ACP after in-depth treatment discussion. Conclusions: Discomfort and logistics were identified as major barriers to ACP. Initiating ACP earlier was identified as a possible solution by clinicians and patients. Feedback obtained will be used to adapt the SICP to be delivered via Telehealth in a single arm pilot study.[Table: see text]
Characteristics of Medicare patients with relapsed/refractory acute lymphoblastic leukemia initiating treatment with inotuzumab ozogamicin, blinatumomab, or other agents.
Authors: Russell-Smith T. Alexander , Shah Richa , Silverstein Alison R. , Petrilla Allison A. , Leinwand Brian , Norris Diane , Schroeder Amy L 
Published: June 2022

e19009 Background: B-cell precursor acute lymphoblastic leukemia (ALL) represents the majority of ALL cases. The INO-VATE and TOWER trials demonstrated that adult patients with relapsed/refractory (RR) B-cell precursor ALL treated with inotuzumab ozogamicin (ino, anti-CD22 monoclonal antibody [mAb]) and blinatumomab (blin, CD19-directed CD3 T-cell engager mAb), respectively, had improved clinical outcomes over chemotherapy. Real-world data on older RR ALL patients initiating CD-targeted therapy is limited. We describe characteristics, healthcare resource utilization (HRU), costs for Medicare beneficiaries with RR ALL initiating ino, blin, or other (chemotherapeutic, tyrosine kinase inhibitor [TKI], or mAb) therapies. Methods: Retrospective study utilizing Medicare enrollment/claims data. Eligible study patients diagnosed with RR ALL 1/1/2017-6/30/2019 and initiated ino, blin, or other at/after diagnosis (first observed treatment = index date). Claims for ino/other patients only visible in outpatient/pharmacy settings; proportion who received inpatient administration prior to outpatient unknown. Blin identifiable in inpatient + outpatient settings. B/T-cell status not captured; patients receiving T-ALL therapy (nelarabine) excluded. Measures included characteristics/HRU during 6 months pre-index and HRU/costs per patient per month (PPPM; costs in 2021 USD) during variable follow-up period (≥3 months until death, disenrollment, or study end). Results: Of 15,586 Medicare beneficiaries with RR ALL, 2,306 (< 15%) initiated an ALL treatment; 1,329 qualified for study inclusion: 55 (4%) received ino, 209 (16%) blin (73% initiated blin during hospital stay), 1,065 (80%) other. Mean age of ino/blin was 62; other 66. Larger proportion of ino cohort qualified for Medicare with non-age-related factors (disability) than blin/other. Treatment groups comparable by sex/race. Ino cohort had higher prevalence of congestive heart, pulmonary, and renal diseases (35%, 31%, 38%) than blin (19%, 25%, 19%), other (23%, 30%, 21%), respectively; diabetes prevalence was lower for ino than for blin/other (20%, 34%, 36%, respectively). Over 6 months pre-index, there was variability in exposure to cytotoxic chemotherapies, mAbs, TKIs by cohort;76% each of ino/blin cohorts, 66% of other cohort were hospitalized for any reason. Follow-up time (months) varied by cohort: 8.0 ino, 12.8 blin, 17.8 other, during which blin patients had higher PPPM rates of hospital stays, longer stays (9.3 days blin, 6.0 ino, 3.9 other), and higher mean (SD) total cost of care: $65,437 ($155,664) blin, $55,995 ($36,688) ino, $17,520 ($22,720) other. Conclusions: During 2017-2019, < 15% of Medicare beneficiaries with RR ALL received ALL treatment, of which 1 in 5 received CD-targeted therapy. Costs were highest for blin followed by ino then other.
Whole-genome sequencing as an alternative to analyze copy number abnormalities in AML, MDS and MM.
Authors: Lyu Xiaodong , Li Tao , Zhu Dandan , Cheng Yuexin , He Xiangxiang , Li Zhenling , Li Shiyong , Geng Shuaipeng , Yao Chunxiao , Li Jingshuai , Li Yangwei , Chang Yinyin , Zhu Zunmin , Mao Mao , Song Yongping 
Published: June 2022

e19023 Background: Genomic alternations especially copy number aberrations (CNAs) are particularly imperative for diagnostic classification and risk stratification in patients with acute myeloid leukemia (AML), myelodysplastic syndromes (MDS) and multiple myeloma (MM). With the technological advances of next generation sequencing (NGS), the current CCA test and the molecular tests are likely to be challenged by whole-genome sequencing (WGS), which is a more unbiased method to detect all types of genomic aberrations. Methods: 178 patients who met the clinical manifestations of blood malignancies were included in the study, including 89 patients with AML, 48 with MDS and 41 with MM. Bone marrow was collected and mononuclear cells were separated to harvest genomic DNA which was sequenced without capture at approximately 1x coverage depth (shallow whole-genome sequencing, sWGS). Genome-wide CNAs greater than 5 Mbp was analyzed for each sample. European Leukemia Net (ELN), Revised International Prognostic Scoring System (IPSS-R) or Revised International Staging System (R-ISS)-defining CNAs were selected and used to assign patients to a genetic risk group through the same classification systems that are used for CCA. Results: In this study, CNA events were identified in 109 (73.6%) patients via sWGS. By calculating frequencies of recurrent gains and losses at chromosome arm level, some recurrent events were detected like gains of chr 8 (observed in 12 AML and 9 MDS patients), chr 1 (observed in 18 MM patients), losses of chr 7 (observed in 9 AML and 3 MDS patients) and chr 13 (observed in 16 MM patients), which were consistent with previously reported cytogenetic events. Besides, amplifications of odd-numbered chromosomes were detected in 15(36.6%) of patients with multiple myeloma, including chromosomes 3, 5, 7, 9, 11, 15, 19 and/or 21. And the trisomy of chr 5, 7 or 9 are mainly observed with a frequency of 66.7%. Among 145 patients with CCA results, a high concordance of 97.7% (98.5%, 97.6% and 97.1% in AML, MDS and MM respectively) was achieved in CNA profiles at individual patient level with cytogenetics and/or FISH. Noteworthily, CNA events were detected in 20 of 28 (71.4%) MM patients with negative karyotyping results. Moreover, sWGS improved the overall diagnostic yield by reassign 18 patients (9 with AML and 9 with MDS) to risk categories with poorer prognosis. Nearly identical CNA profiles from the paired plasma and bone marrow suggest that peripheral blood may serve as a substitute to spare bone marrow aspiration. Conclusions: In summary, a streamlined sWGS provides an accurate, convenient and cost-effective approach to describe genomic profiles of CNAs in patients with AML, MDS and MM. Clinical trial information: ChiCTR2100052276.
Phase II study of lower-intensity frontline therapy for newly diagnosed patients with AML who are unfit or otherwise not eligible for frontline clinical trials.
Authors: Venugopal Sangeetha , Jabbour Elias , Pemmaraju Naveen , Montalban-Bravo Guillermo , Chien Kelly Sharon , Daver Naval Guastad , Jain Nitin , Burger Jan Andreas , Alvarado Valero Yesid , Maiti Abhishek , Dinardo Courtney Denton , Borthakur Gautam , Malla Rashmi , Garcia-Manero Guillermo , Ravandi Farhad , Kantarjian Hagop M. , Kadia Tapan M. 
Published: June 2022

e19028 Background: Pts with newly diagnosed(ND) AML often present with abnormal organ function, poor performance status (PS), concurrent active malignancies, and active infections precluding them from enrolling on frontline clinical trials, since standard eligibility routinely exclude them. We designed a lower-intensity regimen of cladribine plus low-dose cytarabine (LDAC) alternating with decitabine with less stringent inclusion criteria in ND pts unfit or ineligible for existing clinical trials. Methods: Pts >18 years with untreated AML and ineligible for other frontline AML clinical trials were enrolled (NCT01515527). Eligibility criteria included either creatinine ≥2mg/dL; or total bilirubin ≥2 mg/dL; active concurrent cancer, infection, or ECOG PS of 3 or 4; or ineligible for participation in a higher priority protocol. Induction was cladribine 5 mg/m2 IV on D1-5, Cytarabine 20 mg SQ twice daily on D 1-10, followed by consolidation with cladribine 5 mg/m2 IV on D1-3, Cytarabine 20 mg SQ twice daily on D 1-10 alternating with decitabine 20 mg/m2 IV, daily on D 1-5. Primary objective was 60-d survival rate. Results: 25 pts have been enrolled. The median age was 73 yrs (range, 52-82) with 76% aged ≥70 yo. 6 pts (24%) had concurrent active malignancy, 4 (16%) had baseline creatinine >2mg/dL, and 9 (36%) had PS ≥3. 76% were adverse risk per ELN 2017 (Table). Among 25 evaluable pts, 17 (68%) achieved a composite complete response (CRc) including 10 (40%) CR and 7 (28%) CR with incomplete count recovery (CRi). Among responders, 6 pts (35%) achieved MRD neg by flow. Of 7 pts with no response, all were ELN adverse risk. Median cycles to response was 1 (range: 1 - 4). 30- and 60 d mortality was 8% and 16%, respectively, including 2 pts (8%) who died due to pseudomonal sepsis on D8, and the other due to pneumonia on D11. At a median follow up of 9.4 months (range, 0.4- 19.9 m),median OS (6-mo OS% - 61 %), and EFS was 8.3 mo each (6-mo RFS% - 56 %) with a 60-d OS and EFS rate of 83% each, with a median RFS of 5.8 mo (2-mo RFS%-66%; 6-mo RFS% - 49 %). In this challenging patient population, this lower-intensity regimen was well tolerated, with an acceptable toxicity profile. Conclusions: In an unfit patient population of ND AML with high comorbidity burden, that were ineligible for other clinical trials, induction therapy with Cladribine plus LDAC was feasible and effective and can allow pts to achieve remission and move on to effective post-remission therapy. Clinical trial information: NCT01515527. [Table: see text]