bluuebunny/crossref_metadata_2025_split huggingface dataset:
Health outcomes and resource utilization associated with postsurgical opioid use among cancer patients undergoing curative-intent surgery.
Authors: Lin Na , Xu Yuan , Cheung Winson Y. , Quan May Lynn 
Published: June 2021

6515 Background: To date, it remains unclear whether new persistent post-surgical opioid use is associated with subsequent opioid overdose, higher mortality and greater consumption of healthcare resources among cancer patients. To fill this gap, a population-based cohort study by applying real-world data has been performed to compare the long-term outcomes and healthcare resource use between new persistent and non-persistent opioid users among cancer patients after curative-intent surgery. Methods: This retrospective cohort study included all adult cancer patients with solid tumours who received curative-intent surgery in Alberta between 2011 and 2015, with a follow-up period until December 31, 2019. Patients who had multiple tumors, or had a follow-up < 6 months, or > 30 days of hospitalization were excluded. A new persistent post-surgical opioid user was defined as a patient who was opioid-naïve before surgery (no opioid prescription filled prior to the surgery) and subsequently filled at least one opioid prescription between 60 and 180 days after surgery. The outcomes (opioid overdose and mortality within 3 years) and health resource use (emergency department visits and hospitalization within the first year) after surgery were evaluated by applying multivariable logistic and Cox regressions. Results: A total of 19,219 patients received curative-intent surgery with a median follow-up of 47 months, of which 1,530 (8.0%) were identified as postoperative new persistent opioid users. Compared with the non-persistent group, a higher rate of opioid overdose (OR = 1.81, 95% CI: 1.49-2.2) within 3 years of surgery has been observed for new persistent opioid users, who were also associated with a greater likelihood of being hospitalized (OR = 2.52, 95% CI: 2.21-2.87) and visiting an emergency room (OR = 2.0, 95% CI: 1.78-2.24) within the first year after surgery. A higher overall (HR = 1.37, 95% CI: 1.2-1.57) and non-cancer caused mortality (HR = 1.39, 95% CI: 1.18-1.65) has also been detected for new persistent opioid users during the study follow-up period. Conclusions: For cancer patients undergoing curative-intent surgery, reducing new persistent opioid use is imperative to improve subsequent outcomes and health resource utilization.
Significant decline in cancer diagnostic testing in U.S. CMS population during the COVID-19 pandemic.
Authors: Smart Dave , Riccelli Peter , Kerr Keith , Clark Jordan , Fosvig Susanne Munksted , Lawler Mark 
Published: June 2021

6536 Background: The COVID-19 pandemic has caused >400,000 infection related deaths in the US to January 2021. Actions taken to limit COVID-19 infection and mortality could potentially lead to unintended consequences, precipitating excess mortality due to other causes. One such cause is delayed cancer diagnosis. Significant decreases in presentation for cancer diagnosis at the primary care level have been noted in the UK. This study aimed to look for evidence of a similar effect in the US. Methods: CMS claims data from JAN18-JUN20 associated with primary diagnosis across 11 cancers (bladder, breast, cervical, colorectal, endometrial, lung, ovarian, pancreatic, prostate, sarcoma and thyroid) were analyzed for use of surgical pathology (SP), a procedure associated with initial diagnosis, and immunohistochemistry (IHC). Test volumes varied widely by test and cancer so were normalized to enable comparison across indications. This was done by dividing the month-on-month difference for the period JAN19-JUN19 vs JAN20-JUN20 by the median monthly test volume for the period JAN18-DEC19 (“pre-COVID period”). Extent and duration of declines in test rates and number of missing patients as the sum of these declines were then determined. The ratio of IHC to SP testing was taken to determine any decline in likely post-initial diagnosis testing. Results: There were significant (>10%) declines in test volumes for SP for all 11 cancers at some time in Q1-Q2 2020. Table. Extent, duration and return to pre-COVID levels for SP testing across 11 cancers Median extent and duration of the decline was 56% (range 41.1%-80.4%) and 2 months (range 1- >4). This equates to 32,192 missing diagnoses across all cancers. SP test volumes for all cancers except lung and breast had returned to around pre-COVID levels by JUN20. There was no significant (>10%) increase in normalized SP test volume after the COVID dip for any cancer. While SP showed decreased test volumes across all cancers at some point during the first half of 2020, test volume ratios of IHC to SP showed increases for most cancers in the same time period. Conclusions: These data highlight that the decline in patients presenting to their primary care physicians with suspicion of cancer for diagnostic investigation was linked to COVID-19 prevention strategies. No evidence for increased, “catch up” testing to address presentational/diagnostic backlog was observed. Thus, it is predicted that these patients may subsequently present with a more advanced cancer. Potential excess morbidity, mortality and cost associated with absent or delayed diagnosis should be factored into cancer control programs going forward.[Table: see text]
Activity of daily living of elderly patients with gastric cancer after surgery.
Authors: Okuyama Ayako , Mizutani Tomonori , Hamaguchi Tetsuya , Higashi Takahiro , Ogawa Asao 
Published: June 2021

6588 Background: Elderly patients are concerned with the physical burden of cancer treatments. This study aimed at investigating the reduction of the activity of daily living (ADL), length of hospital stay and readmission rate after surgery for gastric cancer. Methods: Insurance claim data linked with hospital-based cancer registries in Japan for gastric cancer patients diagnosed in 2015 from 431 hospitals was used. This data is expected to cover 49.0% of new cancer cases in Japan. To compare the effect of the treatment by age group, we analyzed the reduction of ADL between admission and discharge, length of hospital stay and readmission rate after endoscopic submucosal dissection (ESD) or endoscopic mucosal resection (EMR) for patients with cT1N0M0, and open surgery for patients with cM0. Patients who aged 40 years or older with independent ADL at admission for their first-course treatment was included. ADL was assessed using Barthel index (0-100 points). ADL decrease by 10 points or more was identified as ADL reduction. Results: Overall, 25,521 patients receiving ESD/EMR and 10,527 patients receiving open surgery were identified. ADL reduction after ESD or EMR under 80 years old was less than 1%, while over 80 years old ADL reduction was more than 2.5%. Length of hospital stay (11 days) and unexpected readmission rate (2 to 3 %) was almost similar. ADL reduction after open surgery under 75 years old was less than 3%. This reduction rates have increased with age, 11.5% for over 85 years old. Length of hospital stay also tended to increase by age (21 days for under 65 years old, 29 days for over 85 years old). Unexpected readmission rate for over or 80 years old (1.4%) was slightly higher under 80 years old (less than 1%). Conclusions: The effect of ADL reduction after ESD/EMR was not so significant for patients over 80 years old. While ADL reduction after open surgery tended to increase for aged 80 years and older. Providing these information to elderly patients and their families can be important in deciding treatment options.[Table: see text]
Measurable residual disease response in acute myeloid leukemia treated with venetoclax and azacitidine.
Authors: Pratz Keith , Jonas Brian Andrew , Pullarkat Vinod , Recher Christian , Schuh Andre C. , Thirman Michael J. , Garcia Jacqueline Suen , Dinardo Courtney Denton , Vorobyev Vladimir , Fracchiolla Nicola , Yeh Su-Peng , Jang Jun Ho , Ozcan Muhit , Yamamoto Kazuhito , Illes Arpad , Zhou Ying , Dail Monique , Chyla Brenda , Potluri Jalaja , Dohner Hartmut 
Published: June 2021

7018 Background: In the phase 3 VIALE-A trial, rates of composite complete remission (CRc; complete remission [CR] + CR with incomplete hematologic recovery [CRi]) and measurable residual disease response (MRD<10-3) were higher in patients (pts) treated with venetoclax (Ven) + azacitidine (Aza) compared to Aza alone (23.4%/7.6%, p<0.001). There is limited evidence of the clinical significance of MRD monitoring in pts receiving low-intensity chemotherapy. Herein, we explored the outcomes of pts treated with Ven+Aza who achieved both CRc and MRD<10-3 in the VIALE-A trial (NCT02993523). Methods: Enrolled pts were ≥18 years and unfit for intensive chemotherapy. Pts received Ven 400 mg orally; days 1–28 and Aza 75 mg/m2; days 1-7/28-day cycle. Bone marrow aspirate samples for multiparametric flow cytometry assessments by integrated leukemia-associated immunophenotypes and different than normal procedures were collected for central analysis (Covance Central Laboratory Services) at baseline, end of cycle 1, and every 3 cycles thereafter. Assessments were performed independent of disease responses. MRD response was defined as <1 residual blast /1000 leukocytes (<10-3). CRc, DoR, OS, and EFS were assessed. Disease assessments were per modified International Working Group response criteria for AML. Results: 211/286 (74%) pts treated with Ven+Aza with at least one valid post-baseline MRD assessment were considered MRD evaluable; 78/211 (37%) achieved MRD<10-3 and 133/211 (63%) had MRD≥10-3. Median age (MRD<10-3/ MRD≥10-3) was 76 (range: 49-89)/77 (58-91) yrs. Pts (MRD<10-3/ MRD≥10-3) received median of 14.5 (range: 1-28) /7.0 (1-30) cycles of Ven+Aza. At median follow-up of 22.0 (range: 20.1-23.0)/20.8 (19.8-22.3) months (mos), CRc + MRD<10-3/ MRD≥10-3 was achieved by 67 (86%)/ 97 (73%); 20/67 (30%) achieved CRc + MRD<10-3 by end of cycle 1. Median DoR, OS, and EFS were not reached in pts with CRc + MRD<10-3 response (Table). The 12-mo estimates for DoR, OS, and EFS for pts with CRc + MRD<10-3response were 81.2%, 94.0%, and 83.2%, respectively. Adverse events ≥grade 3 (MRD<10-3/ MRD≥10-3) were febrile neutropenia (50%/43%), neutropenia (50%/35%), and thrombocytopenia (44%/44%), similar to the overall population. Conclusions: Pts with best response of CRc who achieved MRD<10-3 response with Ven+Aza treatment had longer DoR, OS, and EFS than pts who were CRc and MRD positive. Clinical trial information: NCT02993523. [Table: see text]
Distress in a pandemic: The association of the coronavirus disease-2019 (COVID-19) pandemic with distress and quality of life in hematopoietic stem cell transplantation (HSCT).
Authors: Amonoo Hermioni L. , Topping Carlisle E. W. , Clay Madison A. , LeBlanc Thomas William , Greer Joseph A. , Lee Stephanie , Temel Jennifer , El-Jawahri Areej 
Published: June 2021

7032 Background: The global COVID-19 pandemic has drastically disrupted cancer care, potentially exacerbating patients’ distress levels. Patients with hematologic malignancies undergoing HSCT may be especially vulnerable to this pandemic stress given their well-documented heightened psychological distress and impaired quality of life (QOL). However, the association of the COVID-19 pandemic with distress and QOL is not well understood. Methods: We conducted a cross-sectional analysis of data from 205 patients with hematologic malignancies undergoing HSCT who were enrolled in a multi-site, randomized supportive care trial. We compared baseline pre-HSCT distress (depression, anxiety, and posttraumatic stress disorder [PTSD] symptoms) and QOL between participants enrolled pre-COVID-19 (i.e., 03/2019-01/2020) and during the COVID-19 pandemic (i.e., 03/2020-01/2021). We used the Hospital Anxiety & Depression Scale, PTSD Checklist, and Functional Assessment of Cancer Therapy-Bone Marrow Transplant to assess symptoms of depression, anxiety, and PTSD, as well as QOL respectively. We used regression models adjusting for age, gender, race, relationship status, and cancer diagnosis to examine the relationship between the period of enrollment and patient-reported distress and QOL. Results: Prior to COVID-19, 124 participants enrolled, and 81 participants enrolled during the COVID-19 pandemic. The two cohorts had similar baseline demographic and disease risk factors. Most participants were non-Hispanic (n = 185; 90.2%), White (n = 138; 86.3%), and female (n = 131; 64.5%) with a mean (SD) age of 54.9 (11.7) years. In multivariate regression models, enrollment during COVID-19 was not associated with pre-HSCT depression (B = 0.004; 95% CI, -0.02 to 0.03; p = 0.73), anxiety (B = 0.008; 95% CI, -0.01 to 0.03; p = 0.44), PTSD (B = 0.004; 95% CI, -0.004 to 0.01; p = 0.35) symptoms or QOL (B = -0.003; 95% CI, -0.02 to 0.01; p = 0.68). Conclusions: Contrary to the widespread notion that the COVID-19 pandemic has worsened distress in patients with cancer, we found no differences in pre-HSCT distress or QOL in patients with hematologic malignancies undergoing HSCT prior to or during the COVID-19 pandemic. Our findings highlight the need to comprehensively explore the multifactorial causes (e.g., illness experience, treatment burden) of distress and QOL deficits in HSCT recipients irrespective of the COVID-19 pandemic.
Phase 1 trial of anti-CD22 recombinant immunotoxin moxetumomab pasudotox combined with rituximab for relapsed/refractory hairy cell leukemia.
Authors: Kreitman Robert J. , Stetler-Stevenson Maryalice , Yuan Constance , Wang Hao-Wei , Zhou Hong , Raffeld Mark , Xi Liqiang , Arons Evgeny , Feurtado Julie , James-Echenique Lacey , Braylan Raul , Calvo Katherine R. , Maric Irina , Dulau Alina , Pastan Ira 
Published: June 2021

7036 Background: Anti-CD22 recombinant immunotoxin moxetumomab pasudotox (Moxe) is FDA-approved for hairy cell leukemia (HCL) patients who have received at least two prior systemic therapies including a purine nucleoside analog. In phase 3 testing the complete remission (CR) rate was 41%, and response was higher in patients with lower tumor burden and lower titers of antidrug antibodies (ADA). Phase 1 testing indicated that most CRs were without minimal residual disease (MRD) and eradication of MRD was associated with prolonged CR duration. Monoclonal antibody (Mab) rituximab binds to CD20 on HCL cells and induces apoptosis or immune-mediated killing, but as a single-agent achieved only 13% CRs in relapsed HCL requiring therapy. In a phase 1 trial to determine safety, rituximab was combined with Moxe, with the goal to help reduce tumor burden and to prevent or delay ADA by killing normal B-cells. Methods: To allow rituximab sufficient time to accomplish both goals, it was infused 3 days before day 1 of cycle 1 at 375 mg/m2, and Moxe was given by 30-minute infusion on days 1, 3 and 5. On repeat cycles of Moxe days 1, 3 and 5, rituximab was given on day 1. Cycles were generally spaced 4 weeks apart. Moxe was begun at a lower dose, 30 rather than the 40 mcg/kg dose used in phase 3 in case the rituximab would increase its toxicity. Bone marrow aspirate flow cytometry, which can detect 0.002% HCL cells, was the most sensitive test used for MRD detection, much more sensitive than BRAF V600E digital droplet PCR (ddPCR) or bone marrow biopsy immunohistochemistry (IHC). Patients could receive 4 cycles past MRD-free CR, but not more than 8 cycles. Results: Three patients received Moxe at 30 mcg/Kg/dose and 6 received 40 mcg/Kg/dose, all without dose limiting toxicity (DLT). There was no evidence of hemolytic uremic syndrome or capillary leak syndrome. To prevent intravascular hypovolemia due to expected third spacing, patients were encouraged to drink one cup per hour of water or other fluid from days 1 to 8 and take dexamethasone 4 mg orally if headache or nausea prevented good oral hydration. Of the 9 patients, 7 (78%) achieved CR after 2 (n = 6) or 3 (n = 1) cycles, and achieved MRD-free CR after 2 (n = 3), 4 (n = 3) or 6 (n = 1) cycles. No patients became infected with COVID-19. Conclusions: This phase 1 trial met its primary endpoint of determining whether rituximab could be safely combined with Moxe and will enroll 4 additional patients to further access clinical activity. Further testing will determine whether addition of a CD20 Mab to Moxe significantly improves clinical outcome compared to Moxe alone, particularly long-term MRD-free CR rate. Clinical trial information: NCT03805932.
Novel application of Kaplan-Meier methods to model tolerance for nonadherence to imatinib in patients with chronic myeloid leukemia (CML) in the ADAGIO study.
Authors: Obeng-Kusi Mavis , MacDonald Karen , van Lierde Marie-Anne , Abraham Ivo 
Published: June 2021

7038 Background: Although adherence to imatinib treatment has been shown to be critical for attaining treatment response among patients with CML, some studies have suggested a 7.3-9.9% nonadherence tolerance margin before loss of treatment effects. We aimed to model probabilistically the margin of tolerance required to ensure treatment response among patients prescribed imatinib and the margin, if any, before treatment response is at risk. Methods: We performed a post hoc analysis of the ADAGIO study conducted in Belgium on 169 evaluable patients ( Blood 2009). Using the pill count ratio as, what in conventional survival analysis would be, the time variable, we modeled the cumulative likelihood of treatment response as a function of increasing pill count adherence. We applied Kaplan-Meier methods to model the likelihood of complete cytogenetic (CCyR), complete hematological (CHR), major molecular (MMR) and optimal (OR) (as defined by the European Leukemia Net) response as a function of 90-day pill count adherence. Kaplan-Meier methods thus estimated the tolerance for nonadherence to imatinib by calculating the 1 minus Kaplan-Meier estimate for treatment response. Results: Analyses (see Table) showed that ̃100% adherence of prescribed dose is associated with probabilities (rounded) of 0.84 for CHR, 0.83 for CCyR, 0.82 for OR, and 0.77 for MMR; compared to, 0.37 (CHR and CCyR), 0.35 (OR), and 0.39 (MMR) at 90% adherence. (of 0.7698 (MMR). Increasing the intake of imatinib from 90% to 100% of the prescribed dose increased the likelihood of the various treatment responses by 1.95 to 2.35-fold. Conclusions: Our findings challenge any previously estimated tolerance for nonadherence. There is virtually no margin for nonadherence if the objective is to optimize the likelihood of treatment response, and only a minimal margin to avoid impaired treatment response. Under such adherence, response rates similar to those in the pivotal IRIS trial can be obtained. Clinicians must assess and promote patient adherence, and patients must be perfectly adherent.[Table: see text]
Engineered immunostimulatory cells can convert PBMCs from chronic lymphocytic leukemia (CLL) patients into potent tumor killing immune cells.
Authors: Keegan Joshua W. , Borriello Frank , Fernandes Stacey M. , Brown Jennifer R. , Lederer James A. 
Published: June 2021

7517 Background: Alloplex Biotherapeutics has developed a cellular therapeutic that uses ENgineered Leukocyte ImmunoSTimulatory cell lines called ENLIST cells to activate and expand populations of tumor killing effector cells from human peripheral blood mononuclear cells (PBMCs). This process leads to a 300-fold expansion of NK cells, CD8+ T cells, NKT cells, and TCRγδ T cells that are called SUPLEXA cells, which will be cryopreserved and transferred back into patients as an autologous immune cell therapy for cancer. In this study, PBMCs from CLL patients were used to generate SUPLEXA cells as a first approach to comparatively profile SUPLEXA cells from cancer patients and normal healthy volunteers (NHVs). Methods: ENLIST cell lines were engineered by expressing curated immunomodulatory proteins in the SK-MEL-2 melanoma cell line. Two million (M) PBMCs from 10 CLL patients or 2 NHVs were incubated with 0.4 M freeze/thaw killed ENLIST cells for 5 days in XVIVO-15 medium with 2% heat-inactivated human AB serum (XAB2) and then split 1:15 in XAB2 containing IL-7 and IL-15 to expand. After 9 days, SUPLEXA cells were harvested and cryopreserved. Results: Original PBMCs and matched SUPLEXA cells from each donor were thawed and characterized by mass cytometry (CyTOF) using a 47-marker antibody panel. CyTOF staining results of PBMCs from CLL patients demonstrated approximately 95% leukemia cells and few T cells, NK cells, B cells, and monocytes. CyTOF staining of SUPLEXA cells from all 10 CLL patients showed expansion of NK cells (17%), CD8 T cells (11%), and CD4 T cells (7.5%) that were similar in phenotype to SUPLEXA cells from NHVs showing high expression of granzymes and perforin that are indicative of potent tumor cell killing activity. Cancer cells in the original CLL PBMC samples were reduced to 0.78%. However, a population of non-T/non-B cells (60% ± 9.5%) was detected in SUPLEXA cells from all CLL patients that require further characterization. Next, SUPLEXA cells from CLL and NHV patients were comparatively tested for tumor cell killing activity at 2:1, 1:1, and 1:2 effector to target cell (MEL-14 melanoma cells expressing RFP) ratios. Percent killing of tumor cells by SUPLEXA cells prepared from CLL patients (77.8% ± 2.6% at 2:1) and NHVs (81.5% ± 0.3% at 2:1) were nearly identical at all effector to target ratios. Conclusions: We demonstrate for the first time that PBMCs from CLL patients can be converted into SUPLEXA cells despite low numbers of normal immune cells at baseline and the known immunologic impairment present in CLL patients. Importantly, SUPLEXA cells derived from CLL patients acquire potent tumor killing activity that is indistinguishable from SUPLEXA cells prepared from NHVs. Taken together, these findings support the feasibility of converting PBMCs from CLL patients with low percentages of NK and T cells into an autologous cellular therapy for cancer.