bluuebunny/crossref_metadata_2025 huggingface dataset:
A comparison of sleep, insomnia and health-related quality of life between mothers and fathers of preterm versus full-born infants: a longitudinal study from Norway
Authors: Marthinsen Gunhild Nordbø , Helseth Sølvi , Småstuen Milada , Bjorvatn Bjørn , Fegran Liv
Published: June 2024

Background

Poor sleep may negatively affect parents’ health-related quality of life (HRQoL). This longitudinal study aimed to describe and compare sleep, insomnia and HRQoL in mothers and fathers of preterm and full-born infants, and to assess possible associations between sleep, insomnia, and HRQoL from birth up to 12 months in the total sample.

Methods

A longitudinal study of parents of preterm (n = 25 couples) and full-born (n = 76 couples) infants was conducted. To assess sleep, parents wore wrist actigraphs and filled out sleep diaries for 2 consecutive weeks before responding to a digital questionnaire regarding insomnia symptoms and HRQoL. Actigraphy and sleep diary data were collected at the infant age of 2 months, while questionnaire data on insomnia and HRQoL were collected at the infant ages of 2, 6, and 12 months. Statistical analyses included linear regression and linear mixed models for repeated measures.

Results

There were no statistically significant differences in total sleep time (actigraphy and sleep diary) between the parent groups (preterm and full-born) at 2 months postpartum. Sleep efficiency was significantly higher for the full-born group. All mothers reported significantly shorter total sleep time and lower sleep efficiency compared to fathers (all p < 0.01). In the whole sample, insomnia incidence at 2 months postpartum was high (> 43.5%), and for mothers, it remained high at 6 and 12 months (> 50%). No significant HRQoL differences were identified between the parent groups over time. Fathers in both groups reported significantly higher physical HRQoL levels compared to mothers (p = 0.04). There were no significant associations between total sleep time or sleep efficiency and HRQoL at 2 months postpartum. Insomnia symptoms were associated with reduced mental and physical HRQoL at all measurement points.

Conclusions

Sleep efficiency (actigraphy and sleep diary) was significantly higher for the full-born group compared to the preterm group. Mothers (both groups) experienced significantly shorter total sleep time and lower sleep efficiency compared to fathers. The incidences of insomnia symptoms were high at 2 months postpartum for the whole sample and remained high at follow-up for mothers. Fathers (both groups) reported higher physical HRQoL compared to mothers. Insomnia symptoms had a significantly negative impact on parents’ long-term HRQoL.
Translation and reliability and validity of the Chinese version of Amyotrophic Lateral Sclerosis-Specific Quality of Life-Short Form
Authors: Zhang Zhijie , He Xin , Cui Jialu , Wang Jing , Shi Baoxin
Published: June 2024

Objective

To translate Amyotrophic Lateral Sclerosis-Specific Quality of Life-Short Form (ALSSQOL-SF) and test its reliability and validity, so that explore feasibility in Chinese mainland and make up the gap of specific tools for measuring quality of life of patients with ALS.

Methods

This was a cross-sectional design. The Brislin translation model was used to translate ALSSQOL-SF, and the Chinese version of ALSSQOL-SF (C-ALSSQOL-SF) was revised through cultural adaptation and pre-test. The convenience sampling method was used to investigate 138 patients with ALS in Tianjin to test the reliability and validity of the C-ALSSQOL-SF.

Results

The C-ALSSQOL-SF included 20 items, covering 6 dimensions: physical symptoms, bulbar function, negative emotion, interaction with people and the environment, religiosity and intimacy. The scale-level content validity index (S-CVI) of C-ALSSQOL-SF was 0.964, and the item-level content validity index (I-CVI) was between 0.857 to 1.000. The results of Confirmatory Factor Analysis (CFA) showed that CMIN/DF = 1.161, RMSEA = 0.034, GFI = 0.892, IFI = 0.976, TLI = 0.969, CFI = 0.975, and the 6-factor model fitted well. The scores of C-ALSSQOL-SF and WHOQOL-BREF were positively correlated (r = 0.745). The Cronbach’s α coefficient of the scale was 0.85, the Cronbach’s α coefficient of each dimension was between 0.59 to 0.86, and the split-half reliability was 0.78.

Conclusion

The Chinese version of ALSSQOL-SF has good reliability and validity, and can be used as a tool to evaluate the quality of life of patients with ALS in Chinese mainland.
Transition of care in a Danish context: translation, cross-cultural adaptation and content validation of CTM-15 and PACT-M
Authors: Ajstrup Merete , Mejdahl Caroline Trillingsgaard , Christiansen David Høyrup , Nielsen Lene Kongsgaard
Published: June 2024

Background

Transition of care from hospitalisation to home is a complex process with potential patient safety risks, especially for patients with multimorbidity. Traditionally, the quality of transition of care has been evaluated primarily through readmission rates. However, interpreting the readmission rates presents challenges, and readmission rates fail to capture the patient’s perspective on the quality of the care transition. Insight into the patient’s experience with their care or a health service can be provided through the use of patient-reported experience measures (PREMs), and the two PREMs Care Transitions Measure 15 (CTM-15) and Partners at Care Transitions Measure part 1 and 2 (PACT-M1 and PACT-M2) assess on the quality of transition of care from the patients’ perspective. The aim of this study was to translate, culturally adapt, and assess content validity of CTM-15, PACT-M1, and PACT-M2 for Danish-speaking patients with multimorbidity.

Methods

A two-step approach was used for content validation, involving cognitive debriefing and interviews with patients, representing the target group, as well as quantitative data collection from healthcare professionals representing all three sectors of the Danish healthcare system. The patients were systematically interviewed regarding the aspects of content validity; comprehensibility, relevance, and comprehensiveness. The healthcare professionals assessed the relevance and comprehensiveness of each item through questionnaires, allowing the calculation of a content validity index (CVI). An item CVI ≥ 0.78 is considered good.

Results

The results of the qualitative data indicated that both CTM-15 and the PACT-M questionnaires were considered relevant, and comprehensible, and comprehensive to the target group. The CVI computed at item level determined that PACT-M1 and PACT-M2 demonstrated excellent content validity among the healthcare professionals, whereas the CVI for two items of the CTM-15 fell below the threshold value for “good”.

Conclusion

The Danish versions of the PACT-M questionnaires demonstrated good content validity, and the CTM-15 demonstrated acceptable content validity based on qualitative data from patients and quantitative data from healthcare professionals. Further validation of the questionnaires, by assessing their construct validity and reliability is recommended.
Predicting disease recurrence in breast cancer patients using machine learning models with clinical and radiomic characteristics: a retrospective study
Authors: Azeroual Saadia , Ben-Bouazza Fatima-ezzahraa , Naqi Amine , Sebihi Rajaa
Published: June 2024

Background

The goal is to use three different machine learning models to predict the recurrence of breast cancer across a very heterogeneous sample of patients with varying disease kinds and stages.

Methods

A heterogeneous group of patients with varying cancer kinds and stages, including both triple-negative breast cancer (TNBC) and non-triple-negative breast cancer (non-TNBC), was examined. Three distinct models were created using the following five machine learning techniques: Adaptive Boosting (AdaBoost), Random Under-sampling Boosting (RUSBoost), Extreme Gradient Boosting (XGBoost), support vector machines (SVM), and Logistic Regression. The clinical model used both clinical and pathology data in conjunction with the machine learning algorithms. The machine learning algorithms were combined with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) imaging characteristics in the radiomic model, and the merged model combined the two types of data. Each technique was evaluated using several criteria, including the receiver operating characteristic (ROC) curve, precision, recall, and F1 score.

Results

The results suggest that the integration of clinical and radiomic data improves the predictive accuracy in identifying instances of breast cancer recurrence. The XGBoost algorithm is widely recognized as the most effective algorithm in terms of performance.

Conclusion

The findings presented in this study offer significant contributions to the field of breast cancer research, particularly in relation to the prediction of cancer recurrence. These insights hold great potential for informing future investigations and clinical interventions that seek to enhance the accuracy and effectiveness of recurrence prediction in breast cancer patients.
Study of serum calcium and phosphorus levels in chronic kidney disease patients with acute coronary syndrome
Authors: Abass Noher M. , Yousef Ahmed. M. , Sabet Eman A. , Kamal Yasser M. , El-Rashidy Mohamed H.
Published: June 2024

Background

Cardiovascular (CVS) conditions remain the main etiology of death in individuals with chronic kidney disease (CKD) even after control of classic risk factors of cardiovascular disease (CVD).

Aim

This study is to detect the sequalae of serum phosphorus and calcium level abnormalities in individuals with CKD and their relation to occurrence of acute coronary syndrome (ACS) in those cases.

Methods

A cross-sectional work involved 100 individuals with CKD managed with or without dialysis. They were admitted to Internal Medicine Department, Coronary Care Unit of Sohag University Hospital. Each participant had been subjected to full history taking, clinical assessment, and investigations including serum calcium, phosphorus, creatinine, blood urea, parathyroid hormone level, lipid profile, troponin, CK-MB, electrocardiogram, and echocardiography.

Results

A substantial elevation in serum calcium and phosphorus levels was existed in individuals with CKD with ACS group compared to patients with CKD without ACS group (p = 0.026 and 0.001 respectively). The mean calcium/phosphorus ratio was 3.04 ± 2.14 in patients with CKD with ACS group, while it was 2.31 ± 1.17 in patients with CKD without ACS group. A substantial raise in calcium/phosphorus ratio was existed in CKD with ACS group as compared to patients with CKD without ACS group (p = 0.047). ROC curve analysis shows that calcium/phosphorus ratio can predict acute coronary syndrome at cutoff 1.94 with area under the curve 0.652 with sensitivity and specificity that were 77.8% and 52.1% correspondingly (p = 0.007).

Conclusion

A substantial raise in calcium and phosphorus levels was existed in individuals with CKD with ACS group contrasted to individuals with CKD without ACS group. Calcium/phosphorus ratio can predict acute coronary syndrome at cutoff 1.94.

Clinical trial registration number

NCT05134220.
Achieving Secured Medical Network (SMN) through Stateless Mechanism and SkeyM in Medical-Internet of Things (M-IoT)
Authors: S. Nithya , Palanisamy SatheeshKumar , T. Nivethitha
Published: June 2024

Medical Internet of Things (M-IoT) synchronizes medical devices in a network to provide smart healthcare monitoring to doctors and to provide an interactive model for patients. This embedded networked system gained lots of importance in the last few years. Now almost every hospital adopts M-IoT. Though it had a lot of challenges in the initial stages of implementation such as feasibility, accuracy, and autonomy, now it has bridged the flaws with the help of several researchers in this field. But still, M-IoT lags behind in security and privacy aspects due to which attackers can intrude on the network and exploit patients’ health data. By examining the various intensive security threats imposed on M-IoT a unique way of handling and transferring data over the network is proposed in this paper. From our research findings, this would resolve the data security issues in M-IoT and commence the next advancements.
Combination of pirtobrutinib and lentiviral transduced bispecific anti-CD20/CD19 (LV20.19) CAR T-cell therapy to improve outcomes in patients with relapsed/refractory lymphoma.
Authors: Furqan Fateeha , Palen Katie , Johnson Bryon , Kearl Tyce , Hematti Peiman , Longo Walter L. , Hamadani Mehdi , Fenske Timothy S. , Shah Nirav Niranjan
Published: June 2024

7043

Background: Combination trials of BTK inhibitors (BTKi) with CAR-T have suggested potential synergistic benefit by improving CAR-T immunophenotype and clinical outcomes but are limited by increased toxicity. We report immunophenotype, cytokine profile, and patient outcomes with the new non-covalent BTKi, pirtobrutinib (pirto) when given prior to LV20.19 CAR-T and compare the final CAR product to pts who did not receive pirtobrutinib prior to CAR. Methods: Pts received LV20.19 CAR-T as part of a phase 1/2 trial (NCT04186520). Only pts who received pirto £4 weeks prior to apheresis were included. To determine the impact of pirto on LV20.19 CAR-T, we calculated both polyfunctionality (PFA) and polyfunctional strength index (PSI) for each product using the Isoplexis. Descriptive statistics, t-tests and Kaplan-Meier method were used as appropriate. Results: 11 pts received pirto prior to LV20.19 CAR-T (Table). Median age was 65 (50-80) yrs and median prior lines of therapy were 4 (2-8). There were 4 MCL pts, 5 Richter’s (RT)/CLL, 1 MZL and 1 DLBCL. Median duration of pirto was 4 (1-20) mo. Pts were on pirto for a median of 12 (1-22) days prior to apheresis. All except 1 pts received target CAR-T dose. The day 28 ORR was 82% (CR=7, PR=2). After a median follow up of 13 mo, 3 pts died (PD, Covid, Guillain Barre). The median PFS and OS were both 30.8 mo while the 1-year PFS and OS rates were 9 and 15 mo respectively. 9 pts had CRS and 2 had ICANS, all grades 1-2, while 4 had IEC-HS. One pt had afib recurrence and 1 pt had CMV viremia within 30 days of CAR-T. Among the pts with immunophenotypic data (n=10), there were no differences in naïve or more differentiated T-cell percentages in apheresis and final CAR-T products when compared to pts who did not receive pirto before LV20.19 CAR-T (n=57). Although not statistically significant, both PFA (CD4=61.8 vs 59, CD8= 49.8 vs 46.9) and PSI (CD4= 1752 vs 1608, CD8=1299 vs 1079) were higher with pirto pre-treated pts, suggesting a potential trend towards improved CAR-T functionality. Conclusions: These data represent the largest experience of pirto prior to CAR-T apheresis and demonstrate that pirto can be safely used as a bridge to LV20.19 CAR-T without negatively impacting their immunophenotype and potentially improving functionality. These data support our planned phase 1 clinical trial to assess the safety of pirto as bridging and maintenance therapy with LV20.19 CAR-T (NCT05990465). [Table: see text]
Seven-year overall survival analysis from ECHELON-1 study of A+AVD versus ABVD in patients with previously untreated stage III/IV classical Hodgkin lymphoma.
Authors: Ansell Stephen M. , Straus David J. , Connors Joseph M. , Jurczak Wojciech , Kim Won-Seog , Gallamini Andrea , Ramchandren Radhakrishnan , Friedberg Jonathan W. , Advani Ranjana H. , Hutchings Martin , Evens Andrew M. , Savage Kerry J. , Eom Hyeon-Seok , Feldman Tatyana A , Abramson Jeremy S. , Dong Cassie , Savani Bipin N. , Zomas Athanasios , Fenton Keenan , Radford John
Published: June 2024

7053

Background: In ECHELON-1 (NCT01712490), 6-year follow-up (FU) analyses demonstrated significant improvements in overall survival (OS) and progression-free survival (PFS) with A+AVD (brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine) versus ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), with a comparable safety profile. Here, we report data at 7-year median FU. Methods: Analyses of OS and PFS per investigator were conducted in the intent-to-treat (ITT) population (data cut-off March 11, 2023). Patients (pts) were randomized 1:1 to receive ≤6 cycles of A+AVD (n=664) or ABVD (n=670) on days 1 and 15, every 28 days. PET scan after cycle 2 (PET2) evaluation was mandatory. Long-term safety outcomes in the safety population included resolution or improvement of peripheral neuropathy (PN), second malignancies, and pregnancies. Results: At median FU of 89.3 months (95% CI 87.0–90.2), 7-year OS rates were 93.5% (95% CI 91.1–95.2) with A+AVD and 88.8% (95% CI 85.8–91.1) with ABVD; OS favored A+AVD over ABVD (HR 0.62; 95% CI 0.42–0.90; p=0.011). Subgroup analyses showed consistent OS benefit for A+AVD, including in the age <40 years and Stage IV disease subgroups (Table). 7-year PFS rates with A+AVD vs ABVD were 82.3% (95% CI 79.1–85.0) vs 74.5% (95% CI 70.8–77.7; HR 0.68 [95% CI 0.53–0.86]; p=0.001). PN improved/resolved in most pts at last FU (A+AVD: 86%; ABVD: 87%). Median (range) time to complete resolution of PN (A+AVD vs ABVD) was 16 (0–373) vs 10 (0–343) weeks; median (range) time to improvement was 42 (2–182) vs 19 (15–142) weeks. PN was ongoing in 28% (4% grade ≥3) of A+AVD and 20% (1% grade ≥3) of ABVD pts. Second malignancies were reported in 5% of A+AVD and 6% of ABVD pts. Pts and their partners reported 84/92 livebirths/pregnancies with A+AVD and 59/73 with ABVD; no stillbirths were recorded. Conclusions: At 7-year median FU, pts with stage III/IV cHL who received A+AVD showed a sustained PFS and OS benefit vs ABVD, with PFS rates indicating potential curability. The safety profile in pts treated with A+AVD showed no new safety signals at 7 years. Clinical trial information: NCT01712490 . [Table: see text]
P-GEMOX with sequential or sandwiched radiotherapy for early-stage extranodal natural killer/T-cell lymphoma.
Authors: Xie Mixue , Jiang Qi , Zhao Feng , Zhou De , Tong Hongyan
Published: June 2024

7075

Background: Combined modality therapy (CMT), namely chemotherapy combined with radiotherapy, has been recommended for patients with localized extranodal natural killer/T-cell lymphoma (ENKTL). However, the optimal CMT has not been fully clarified. As chemotherapy is more easily accessible than immediate radiotherapy in the routine clinical practice, the “chemotherapy-first” CMT including sequential or sandwiched radiotherapy deserves further exploration. In addition, the optimal non-anthracycline-based regimen needs to be confirmed. Methods: The P-GEMOX regimen was administrated as follows: pegaspargase 2000 IU/m2 intramuscular on day 1, gemcitabine 1000 mg/m2 intravenous on day 1 and 8, oxaliplatin 130 mg/m2 intravenous on day 1 and was repeated every 21 days. Patients who achieved at least stable disease (SD) subsequently underwent involved field radiotherapy (IFRT). The dose of IFRT ranged from 50 to 55 Gy. Performing sequential radiotherapy (4 cycles of CT+RT) or sandwich radiotherapy (2 cycles of CT+RT+2 cycles of CT) is determined by the clinician based on the patients' conditions. The primary endpoint was the overall response rate (ORR) after 2 cycles of chemotherapy, and secondary study endpoints were CR, PFS, and OS. Safety was also evaluated. Results: From August 2020 to April 2023, thirty-seven patients (23 men, 14 women; median age: 55, 26-76 years) with stage I/II ENKTL who had received P-GEMOX were collected. 14 patients were stage IE and 23 were IIE. ALL patients completed at least 2 cycles of P-GEMOX, which resulted in 94.6% (35/37) of ORR including 30 patients with CR and 5 patients with PR. Among the patients in remission, 15 patients received sequential radiotherapy, 15 received sandwich radiotherapy, 4 were waiting for or in the process of radiotherapy, and 1 patient progressed before radiotherapy. With a median follow-up of 14.8 months (range: 2.6-38.1 months), the 3-year PFS and OS were 87.2% (95%CI 69.3%-95%) and 90.6% (95%CI 72%-97.1%), respectively. Sandwich radiotherapy had an obvious trend for longer PFS than sequential radiotherapy (18moths-PFS 100% vs. 78%; P=0.073). During the treatment, 21.6% (8/37) of the patients experienced grade 3–4 treatment-emergent adverse events (TEAEs). The most grade 3–4 hematological TEAEs were neutropenia (7/37, 18.9%) and thrombocytopenia (4/37, 10.8%). As for grade 3–4 non-hematological TEAEs, elevated aminotransferase, hyperbilirubinemia and hypofibrinogenemia were 16.2%, 10.8% and 8.1%, respectively. The adverse events of this CMT were well-tolerated and manageable. No treatment-related death occurred. Conclusions: Our study demonstrated that CMT consisted of P-GEMOX showed favorable efficacy with acceptable toxicity, and sandwich radiotherapy (CT+RT+CT) seems give more favorable PFS than sequential radiotherapy. The CMT protocol could be an effective treatment option for early-stage ENKTL patients.
Efficacy of venetoclax-dexamethasone (VenDex) v pomalidomide-dexamethasone (PomDex) in patients (Pts) with t(11;14)-positive relapsed/refractory multiple myeloma [t(11;14)+ RRMM]: Phase 3 CANOVA study biomarker subgroup analysis.
Authors: Bahlis Nizar J. , Popat Rakesh , Beksac Meral , Dimopoulos Meletios Athanasios , Gatt Moshe E. , Gay Francesca , Jo Jae-Cheol , Kapoor Prashant , Kortüm Martin , Ling Silvia , Nagarajan Chandramouli , Suzuki Kenshi , Onishi Maika , Dail Monique , Rossi Emily , Luo Xizhi (Adam) , Arriola Emma Louise , Bueno Orlando Felix , Ross Jeremy A. , Mateos Maria-Victoria
Published: June 2024

7510

Background: The randomized Phase 3 CANOVA study’s (NCT03539744) primary analysis showed multiple numerically improved efficacy endpoints with VenDex v PomDex, but the primary endpoint of mPFS by IRC was not statistically significant. Here, we report correlative biomarker analyses from CANOVA. Methods: CANOVA is a randomized, global, open-label Phase 3 study of VenDex v PomDex in pts with t(11;14)+ RRMM and ≥2 prior lines of therapy (LOTs). The primary endpoint was mPFS by IRC. Key secondary endpoints included ORR, ≥VGPR, mOS, and MRD negativity (<10-5). In post hoc mPFS sensitivity analysis, disease progression, death, and start of next LOT were defined as events. BCL2 gene expression by RNAseq (3.7 log2 FPKM prespecified median cutoff for BCL2high v BCL2low) and chr1q abnormalities by whole-exome sequencing (normal, gain, or amp) were assessed centrally from pretreatment, CD138-enriched BM aspirates. Results: mPFS, post hoc mPFS, and mOS in the VenDex arm were similar by BCL2 status, with numerically higher ORR, ≥VGPR, and MRD negativity rates in the BCL2highsubgroup. In contrast, mPFS and mOS within the PomDex arm were numerically longer in the BCL2lowsubgroup, despite equal ORR in both subgroups (Table). Presence of 1q abnormalities was evenly distributed across BCL2high v BCL2low subgroups in the VenDex arm (51% v 45%) but not in the PomDex arm (59% v 31%). Normal 1q and gain(1q) subgroups had numerically improved mPFS, mOS, ORR, ≥VGPR, and MRD negativity with VenDex; pts with amp(1q) had poor outcomes regardless of treatment, albeit the sample size was small. Conclusions: Pts with BCL2high or gain(1q) had numerically improved clinical efficacy with VenDex v PomDex. Clinical benefit was consistent across BCL2 subgroups ( BCL2high or BCL2low) with VenDex but not PomDex. Pts with amp(1q) fared poorly irrespective of treatment arm. Clinical trial information: NCT03539744 . [Table: see text]
Characterization of the BCMA epitope bound by BCMA-CD3 T cell engager elranatamab.
Authors: Josic Maria , Schweibold Reece , Mosyak Lidia , Chaparro-Riggers Javier , Baaten Bas , Bompiani-Myers Kristin
Published: June 2024

7546

Background: Elranatamab is a BCMA-CD3 bispecific antibody with an accelerated approval in the US and EU for relapsed/refractory multiple myeloma (RRMM). Elranatamab binds to CD3 on T cells and BCMA on MM tumor cells; this dual binding results in T cell activation, cytokine release, and tumor cell killing. Engagement of the BCMA surface receptor by its ligands, APRIL and BAFF, mediates plasma cell proliferation and survival. Elevated BCMA, as well as BAFF and APRIL are present in MM patients, yet in vitro functional assays have shown physiologically relevant soluble APRIL or BAFF concentrations did not significantly impact elranatamab activity. Moreover, emerging clinical data from relapsed patients has identified novel, yet relatively rare BCMA protein mutations that may impact BCMA ligand or targeted modality binding. Here we characterized the BCMA binding affinity, evaluated the impact on BCMA binding to BAFF and APRIL interactions, and identified the BCMA binding epitope. We also generated a model from crystal structure data to map reported BCMA mutations identified in patients. Methods: Elranatamab binding affinity to recombinant human BCMA and characterization of BAFF and APRIL interactions with elranatamab-bound BCMA were calculated via SPR at 37˚C with a classical sandwich format. The elranatamab BCMA binding epitope was identified by a co-crystal structure with a parental anti-BCMA Fab that has identical CDR sequences to elranatamab. Alpha-fold modeling was used to map identified BCMA mutations on the antibody/BCMA interface. Results: Elranatamab binds to BCMA with higher affinity (~38 pM) compared to reported binding affinities of BAFF (μM range) and APRIL (nM range) ligands. The identified elranatamab epitope largely overlaps with known ligand epitopes, supporting that elranatamab higher affinity BCMA binding blocks ligand binding. Alpha fold modeling of four recently reported rare BCMA mutations shows that they lie along the binding interface. Conclusions: Due to its high affinity for BCMA, elranatamab potency is unlikely to be impacted by elevated levels of soluble BAFF or APRIL in RRMM patients. Future studies are needed to characterize the impact of emerging MM patient BCMA mutations on the binding and function of anti-BCMA targeting modalities, particularly given the small extracellular domain of BCMA available for therapeutic targeting and the highly overlapping binding epitopes reported for approved BCMA agents.
The association between osimertinib and nutritional deficiency among patients with non-small cell lung cancer.
Authors: Tang Zhiting , Chiang Cho Han , Chang Yu-Cheng , See Xin Ya , Wang Qian , Dowlati Afshin , Chiang Cho Hung , Chi Kuan-Yu
Published: June 2024

8031

Background: Osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), is the standard-of-care in EGFR mutation-positive non-small-cell lung cancer (NSCLC) in various settings. Osimertinib commonly causes gastrointestinal adverse effects thereby potentially leading to nutritional deficiencies. Therefore, we aim to evaluate the association between the use of osimertinib and nutritional deficiencies among patients with NSCLC. Methods: We performed a retrospective, propensity score matched study using the TriNetX database, a network comprising deidentified data across more than 120 participating healthcare institutions. We included patients with NSCLC who received either osimertinib or other EGFR-TKIs (afatinib, dacomitinib, erlotinib, gefitinib). The outcomes of interest included vitamin B deficiency, vitamin D deficiency, iron deficiency as well as associated anemia including vitamin B12 deficiency anemia, folate deficiency anemia, and iron deficiency anemia within 5 years of EGFR-TKI initiation. Results: We matched 4264 patients who received osimertinib to patients who received other EGFR-TKIs. In Cox proportional hazard analysis, osimertinib was associated with a 50% higher risk of vitamin B deficiency (Hazard ratio, 1.52 [95% CI: 1.07-2.16]) compared to other EGFR-TKIs. Consistent with this observation, osimertinib was associated with an increased risk of vitamin B12 deficiency anemia and a tendency towards folate deficiency anemia. We also noted a 2-fold higher risk of vitamin D and 5-fold higher risk of iron deficiency in the osimertinib cohort. Consistent with this observation, osimertinib was associated with an increased risk of iron deficiency anemia compared to other EGFR-TKIs. Conclusions: The use of osimertinib is associated with a higher risk of nutritional deficiencies and associated anemias compared to other EGFR-TKIs. One potential explanation is the extended duration of osimertinib therapy, driven by its potent anti-cancer effects. Therefore, it is advisable to consider screening for specific nutritional deficiencies in individuals receiving osimertinib therapy. [Table: see text]
Updated results from COAST, a phase 2 study of durvalumab (D) ± oleclumab (O) or monalizumab (M) in patients (pts) with stage III unresectable non-small cell lung cancer (uNSCLC).
Authors: Aggarwal Charu , Martinez-Marti Alex , Majem Margarita , Barlesi Fabrice , Carcereny Enric , Chu Quincy S. , Monnet Isabelle , Sanchez Alfredo , Dakhil Shaker R. , Camidge David Ross , Pillet Marine , Brown Miranda , Dowson Adam , Cooper Zachary A. , Kumar Rakesh , Herbst Roy S.
Published: June 2024

8046

Background: D consolidation after concurrent chemoradiotherapy (cCRT) improves survival in pts with uNSCLC. Rational immunotherapy combinations may further improve outcomes. As radiotherapy can induce expression of CD73, HLA-E (NKG2A ligand), and PD-L1 in tumor cells, all of which suppress antitumor immunity, there is a rationale for blockade of these immune checkpoints after cCRT. Interim results from COAST (NCT03822351), a global, open-label, Phase 2 study of D ± M (anti-NKG2A) or O (anti-CD73) as consolidation therapy in pts with Stage III uNSCLC, suggested improved progression free survival (PFS) with D+O and D+M vs D alone. We present updated efficacy and safety. Methods: Pts with histologically / cytologically documented Stage III uNSCLC and ECOG PS 0 / 1 with no progression after cCRT were randomized (1:1:1; stratified by histology) within 42 days post cCRT to receive D 1500 mg IV every 4 weeks (Q4W) for 12 months ± O 3000 mg IV Q2W for two cycles then Q4W or M 750 mg IV Q2W. Primary endpoint: objective response rate (ORR). Key secondary endpoints: safety, PFS, and overall survival (OS). Results: From Jan 2019 to Jul 2020, 186 of 189 randomized pts received treatment. Baseline characteristics were generally balanced across arms. As of Jul 18, 2023, median follow-up was 30.1 mo (range, 0.4–48.9). Of pts receiving D, D+O, and D+M, 69.7%, 44.1%, and 41.0% discontinued treatment (Tx), primarily due to progressive disease (42.4%, 18.7%, and 19.6%) or adverse events (AEs; 15.2%, 15.3%, and 14.8%). Median exposure was 7 cycles (range, 1–13) for D, and 13 (1–13) for D+O and D+M. ORR, PFS, and OS (39.6% maturity) are summarized in the Table. Tx-emergent AEs occurred in 98.5%, 96.6%, and 100% (Grade [G] 3/4: 34.8%, 33.9%, and 32.8%) of pts receiving D, D+O, or D+M, respectively; immune-mediated AEs (imAEs) occurred in 34.8%, 25.4%, and 34.4% (G 3/4: 3.0%, 0%, and 3.3%); and the AE of special interest pneumonitis occurred in 16.7%, 20.3%, and 18.0% (G 3/4: 0%, 0%, and 1.6%). Subgroup analyses and biomarker data will be presented. Conclusions: D+O and D+M increased ORR and prolonged PFS and OS vs D alone. Safety was similar across arms, with no new safety signals. Further investigation of D, D+O, and D+M in this population is ongoing in the Phase 3 PACIFIC-9 study (NCT05221840). Clinical trial information: NCT03822351 . [Table: see text]
Prospective monitoring for immunotherapy by liquid biopsy and signal pathway alterations in head and neck cancers.
Authors: Kano Yoshihito , Noji Rika , Naito Takahiro , Fujiwara Shun , Ikeda Sadakatsu , Mori Takehiko , Harada Hiroyuki , Suenaga Mitsukuni
Published: June 2024

e18000

Background: Clinical biomarkers that predict response or prognosis to immune checkpoint inhibitors (ICIs) are unclear in head and neck squamous cell carcinoma (HNSCC). Comprehensive genome profiling (CGP) testing including liquid biopsy using cell-free DNA (cfDNA) has become clinically available; however, CGP testing is approved only once per patient under the Japanese health insurance system. Therefore, whether liquid biopsy is useful for detecting sequential genetic change and disease progression as a real-time monitoring tool is still unknown. This study aims to analyze the cfDNA in the plasm of recurrent or metastatic (R/M) HNSCC patients during ICI therapy. This study was prospectively conducted to examine the relationship between sequential genetic changes and treatment response. Methods: In this prospective study, we examined ten evaluable R/M HNSCC cases treated with ICI monotherapy (nivolumab or pembrolizumab) from October 2020 to December 2023. Blood samples were collected and analyzed using Guardant360 at differing three-time points (0, 4, and 24 weeks or at progressive disease, PD). Results: The ten cases consisted of 5 males and 5 females, with a median age of 71 years old (52-92 years old). Seven patients received pembrolizumab as a first line and three received nivolumab as the second line treatment. The best response to ICI was partial response (PR) in 3 cases , stable disease (SD) in 1 and PD in 6. Three cases discontinued the study at the second point because of the rapid disease progression. Microsatellite status is stable in all cases. Eight of the ten cases had at least one pathogenic mutation, one case had only variants of unknown significance, and one case that had target lesions at lung metastases had none of them through a series of liquid biopsies. The most frequent gene alterations observed were TP53 (60%), TERT promoter (20%), GNAS (20%), and EGFR amplification (20%). In particular, EGFR amplification had emerged at the second point in two PD cases and these patients showed the sensitivity to cetuximab-based therapy at the following treatment line. In all PD cases, the highest variant allele fraction (VAF) was increased at the second point, which might help predict the response to ICI therapy. In one case achieving PR, BRAF mutation had emerged at the second point. Then it was undetectable at the third point with PD, and GNAS mutation was newly detected. In another case, APC inactivation had disappeared at the second point with PR, even though GNAS mutation emerged, and this case maintained the response to ICI. These results suggest that switching the signals in the MAPK or Wnt pathway could impact the response to ICI therapy. Conclusions: The findings of this prospective study demonstrated that the highest VAF alterations and genetic mutations detected by cfDNA analysis could reflect and predict the response to ICI.
A multicenter, retrospective study analysis: Evaluating the efficacy and safety of pembrolizumab in the first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma.
Authors: Hu Man , Zhang Shichuan , Han Yaqian , Wu Hui , Gao Jin , Wu Haijun , Lin Qin , Shang Wei , Li Xia , Feng Hong , Qiao Qiao , Hu Guangyuan , Yang Kunyu , Song Xicheng , Cao Yuandong , Kang Min , Wang Ruozheng , Yu Jinming
Published: June 2024

e18013

Background: PD-1-based therapy has become the first-line standard treatment for R/M HNSCC, but KN-048 lacked data on the mainland Chinese population. This study aims to conduct a pooled analysis of the efficacy and safety of first-line pembrolizumab-based therapy in patients (pts) with R/M HNSCC from different regions in China. Methods: Data comes from 17 hospitals. R/M HNSCC pts who received pembrolizumab alone or in combination with chemotherapy/targeted therapy from July 2020 to Jan 2023 were reviewed by searching the hospital HIS/medical record system. The primary endpoint of was OS, and secondary endpoints include time of pembrolizumab treatment (TOPT), safety, etc. Investigators also explored the impact of different biomarkers on survival. This study used SPSS 29 to analyze the data. Results: Total 160 pts were included. Median age was 60 yrs. 81.2% of pts was male, 95% of pts had an ECOG 0-1 . Main primary tumor site showed: oral cavity (60.6%), larynx (12.5%), oropharynx (10.6%). 88.8% of pts had undergone surgery in the past, and 65% received RT. The proportion of pts with only recurrence reached 75.6%. 79 (90.8%) had CPS of 1 or more and 44 (50.6%) had CPS of 20 or more. Other baseline information could be seen in the table. The median follow-up time was 18.5 mos. 70.6% of pts received pembrolizumab combined with chemotherapy, 17.5% received pembrolizumab alone. 48 pts subsequently received second-line treatment, more than half of which were target-based treatments. The median OS of all pts was not reach, among which the mono group vs. combination chemotherapy group (p=0.254). 18mo-OS of monotherapy was 69%, while 61% in combination. No statistical difference was seen in mTOPT (6.0 vs 4.7 mos, p=0.644). The results of the Cox Proportional Hazards Model suggest that ECOG score, smoking history, previous RT and distant metastatic of tumors were related to OS. Primary tumor location, T stage, EGFR mutation related to TOPT. Studies have not found a significant correlation between CPS and survival prognosis. 28.1% of pts experienced TRAEs, the most common of which was G1-4 myelosuppression (33.3%). The main TRAEs of G3-4 were pneumonia (11.1%), bone marrow suppression (8.9%) and abnormal liver function (4.4%). No patient died due to TRAEs. Conclusions: The data reflects that the real-world mOS with local recurrence as the main population was significantly higher than KN-048, and some clinical indicators related to prognosis were also found. In the future, the data of pembrolizumab in R/M HNSCC will be further explored to find more valuable biomarkers. [Table: see text]
Clinicians' perspectives of barriers and facilitators of suicide screening in head and neck cancer care.
Authors: Osazuwa-Peters Nosayaba , Mwobobia Judith , Fish Laura J. , Falkovic Margaret , Benvenisti Revital , Lee Walter T. , Brownson Ross , Rosenstein Donald L. , Goldston David B.
Published: June 2024

e18023

Background: Patients with head and neck cancer (HNC) face a heightened risk of suicide, surpassing rates in other cancers and the general population. Unfortunately, there are currently no suicide-specific clinical guidelines in oncology, and it is unclear what barriers and facilitators impact suicide screening initiatives in HNC care. This qualitative study explored experiences, barriers and facilitators of suicide screening and management of mental health concerns in a diverse group of HNC clinicians. Methods: We conducted qualitative interviews with 16 HNC clinicians at a single healthcare system, including head and neck surgeons, radiation oncologists, medical oncologists, and nurses/nurse practitioners/physician assistants. Interviews covered topics such as clinicians’ perspective of the impact of HNC on patients’ mental health, experience with suicide risk assessment, existing protocols, and overall experiences related to managing mental health concerns in patients with HNC. Using rapid analysis techniques, we identified common challenges, facilitators, and training needs. Results: Our study uncovered distinct barriers faced by HNC clinicians. Key themes included the notable absence of formal suicide and mental health training among HNC clinicians; critical gaps in clinician education and the lack of established protocols for appraising and managing mental health concerns, particularly those related to suicide risk. Other barriers identified included clinicians’ uncertainties in recognizing and addressing suicidal thoughts, limited familiarity with available screening tools, and insufficient resources for patient support. Some key facilitators also emerged, including longer clinic visit times, mental health discussions in interdisciplinary conferences, and greater accessibility of mental health services for comprehensive patient support. Conclusions: In this qualitative study, we observed important barriers in mental health support and service delivery for HNC patients, especially gaps in clinician training, and lack of knowledge of existing suicide-related protocols. Given the suicide burden in HNC, it is important to address these challenges and begin developing initiatives for clinician training and formalized protocols to enhance mental health care for HNC patients.
A nationwide analysis of inpatient mortality for patients with leukemia with iron deficiency anemia.
Authors: Adegbite Benjamin Olufemi , Cytryn Lawrence
Published: June 2024

e18521

Background: Leukemia consists of multiple diverse disorders which confer varying morbidities and an increased risk of mortality. Iron deficiency anemia (IDA) is much more common, and while non-malignant, has also been shown to have an association with increased mortality. Despite the probability of these two hematological conditions coexisting, the interaction between them has yet to be closely studied. This retrospective cohort study aims to help elucidate how IDA affects mortality in patients with leukemia. Methods: Data was obtained from the 2017 – 2019 versions of the National Inpatient Sample (NIS) database from the Healthcare Cost and Utilization Project (HCUP) using ICD-10 codes. Patients with all forms of leukemia were identified and then placed into 4 categories: acute myeloid leukemia (AML), acute lymphocytic anemia (ALL), chronic myeloid leukemia (CML), and chronic lymphocytic leukemia (CLL). Lastly, a multivariate regression model was used (adjusted for age, sex, race, median household income based on patient ZIP code, Charleston Comorbidity Index score, hospital region, hospital teaching status based on rural/urban setting) to calculate the adjusted odds ratio (aOR) for the association between the presence of IDA and inpatient mortality. A significance level of p < 0.05 was used throughout. Results: The sample population consisted of leukemia patients with or without IDA. In total, there were 162,873 patients with all ICD-10 coded forms of leukemia, with 5,710 (3.51%) having IDA. Furthermore, this cohort was found to be older than non-IDA leukemia patients (71.1 ± 0.45 years and 59.2 ± 0.71 years with p < 0.05, respectively). With inpatient mortality as the outcome, the multivariate regression analysis performed for the entire sample showed that the odds of mortality while having IDA was 0.65 times that of not having IDA (95% CI 0.56 – 0.76, p < 0.001). When the analysis was then applied to each of the 4 leukemia categories, the IDA cohort still had lower odds of mortality with CLL (aOR 0.73, 95% CI 0.56 – 0.96; p = 0.024). Conclusions: The analyses show that iron deficiency anemia was generally not associated with increased mortality among leukemia patients, particularly those with CLL. This seemingly counterintuitive result warrants further research to confirm these findings and explore possible underlying mechanisms.
In-hospital outcomes of autologous stem cell transplantation in patients with multiple myeloma with versus without heart failure.
Authors: Garcia Gustavo , Rosario Manuel , Vasquez Moises , Hameed Maha , Vargas Ian , Wiese-Rometsch Wilhelmine , Smith Robert , Nair Jayan
Published: June 2024

e19511

Background: Autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM) is known to improve progression-free survival. However, the outcomes in patients with heart failure (HF) are uncertain. This study aims to compare hospital outcomes in patients with MM undergoing ASCT with and without HF. Methods: The National Inpatient Sample database was used to identify patients with MM undergoing ASCT during hospitalizations between 2016 and 2020. Under IRB exemption, data was extracted using ICD-10 codes. Data were stratified between patient with and without HF. A multivariate regression model was used to estimate the association of HF with ASCT in hospital outcomes, adjusting for statistically significant comorbidities. Results: A total of 30,375 hospitalizations with a diagnosis of MM undergoing ASCT were included, of which 1,535 had HF. On multivariant analysis compared to hospitalization without HF, those with HF had significantly higher risk of in-hospital mortality (adjusted odds ratio [aOR]: 2.20, 95% confidence interval [CI]: 1.49-3.24), graft-versus-host disease (GvHD) (aOR: 4.02, 95% [CI]: 2.48-6.52), transplant complications (aOR: 2.03, 95% [CI]: 1.62-2.56), sepsis (aOR: 2.279, 95% [CI]: 1.95- 2.65), septic shock (aOR: 3.49, 95% [CI]: 2.71-4.48), cardiogenic shock (aOR: 5.33, 95% [CI]: 2.61- 10.9), cardiac arrest (aOR: 3.78, 95% [CI]: 2.24- 6.35) and ventricular arrhythmia (aOR: 2.81, 95% [CI]: 2.08- 3.78). All p-values were <0.001. Additionally, patients with HF had a longer average length of stay (20.48 vs 16.38 days, p< 0.001) and a higher total cost of hospital stay ($245,831 vs $198,732, p<0.001) compared to those without HF. Conclusions: Our findings demonstrated that patients with multiple myeloma undergoing autologous stem cell transplantation, while also having coexisting heart failure (HF), experienced worse outcomes compared to patients without HF. These patients had a higher risk of transplant complications, GvHD, sepsis, septic shock, cardiogenic shock, cardiac arrest, ventricular arrhythmias and mortality. Additionally, these patients experienced a longer hospital stay with higher healthcare costs. Further interventions and research are warranted to improve outcomes in this group of patients.
Multiple myeloma in the African American population: A 2010-2020 NCDB analysis.
Authors: Neupane Niraj , Singh Harkarandeep , Budhathoki Pravash , Joshi Utsav , Shrestha Asis , Shikhrakar Shreeja , Parajuli Aakriti , Prasad Apurwa , Dhakal Binod
Published: June 2024

e19531

Background: Multiple myeloma (MM) exhibits a disproportionately higher prevalence among African American individuals. Various factors contribute to the disease's progression, severity, and prognosis. This analysis presents real-world data from the National Cancer Database (NCDB) from 2010 to 2020. Methods: Cohort of 241,446 MM patients between 2010 and 2020 were analyzed. Demographic variations, including age, gender, insurance status, educational attainment, and median household income, were examined. Multivariate Cox regression analysis was conducted to identify factors influencing survival outcomes. Results: Within the database, from 2010 to 2020, 51,668 cases of multiple myeloma were recorded among Black individuals. The age group most affected was 40 to 65 years (50.2%), followed by those over 65 (47.3%), with 2.5% falling between 18 to 40 years, and a mean age of 64.4 years. Most cases affected females (51.5%), with most households earning less than $40,227 annually. A significant portion of Black patients did not receive a transplant (83.8%) or immune based option (73.1%). The mean duration from diagnosis to therapy initiation was 37.5 days. Multivariate analysis revealed that patients over 65 had a worse prognosis (HR = 1.52, 95% CI: 1.47 – 1.57, P < 0.001) compared to those under 65, while females exhibited a better prognosis (HR = 0.88, 95% CI: 0.86 – 0.91, P < 0.001). Patients with private insurance had better outcomes (HR = 0.73, 95% CI: 0.68 – 0.78, P < 0.001), as did those treated in academic centers (HR = 0.89, 95% CI: 0.87 – 0.92, P < 0.001). Additionally, patients receiving any form of transplant had better outcomes (HR = 0.45, 95% CI: 0.42 - 0.49, P < 0.001), along with those undergoing chemotherapy (HR = 0.73, 95% CI: 0.68 – 0.78, P < 0.001) and immunotherapy (HR = 0.67, 95% CI: 0.64 – 0.69, P < 0.001). Conclusions: The analysis highlights significant demographic and treatment influences among African American patients with MM. Some identifiable factors associated with improved outcomes include younger age, female gender, private insurance, treatment in academic centers, and most importantly receipt of transplant and Immunotherapy. These findings underscore the importance of targeted interventions considering various factors and improving outcomes in this population. [Table: see text]