Disease-related Symptoms Research Articles

Validity and Reliability of the Turkish Version of National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Ovarian Symptom Index-18 (NFOSI-18) and Neurotoxicity-4 (NTX-4) for Patients with Advanced Ovarian Cancer

Objectives. The aim of this study was to investigate the validity and reliability of the Turkish version of the National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Ovarian Symptom Index-18 (NFOSI-18) and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group Neurotoxicity 4-item (NTX-4) in patients with advanced ovarian cancer (OC). Methods. Ninety-four women with OC were included. Pearson correlation coefficients were used to examine the convergent validity between the European Quality of Life Survey-5 Dimension-3 Level (EQ-5D-3L) and the Turkish NFOSI-18 and NTX-4. The internal consistencies of the Turkish NFOSI-18 and NTX-4 were calculated using Cronbach’s alpha. Turkish NFOSI-18 and Turkish NTX-4 were readministered to 62 (67.4%) patients with OC after 14–21 days to evaluate test-retest reliability.Results. Turkish NFOSI-18 and Turkish NTX-4 showed excellent internal consistency (Cronbach’s alpha: 0.919 and 0.917, respectively). The test-retest reliability of Turkish NFOSI-18 and Turkish NTX-4 was detected as good to excellent for total score (ICC [95%] = 0.93 [0.88-0.95] and ICC [95%] = 0.90 [0.85-0.94], respectively). Significant correlations were detected between the EQ-5D-3L total score, NFOSI-18 (r = 0.648, p < 0.01), and NTX-4 (r = 0.694, p < 0.01) indicating sufficient convergent validity. Conclusion. The Turkish NFOSI-18 and Turkish NTX-4 are reliable and valid tools to assess disease-related symptoms in patients with advanced OC.

Anxiety and Health Literacy Levels of Patients Undergoing Colonoscopy.

This descriptive, correlational study was conducted to determine the anxiety and health literacy levels of patients undergoing colonoscopy and the variables affecting them. The study population consisted of individuals who presented for colonoscopy to the endoscopy department of a state hospital. The sample consisted of 160 individuals who met the inclusion criteria. Three data collection tools (Identifying Information Form, State-Trait Anxiety Inventory, and Health Literacy Scale) were used to determine anxiety and health literacy levels. Findings show that the state-trait anxiety of individuals who would undergo colonoscopy for the first time was moderate, and their health literacy scores were inadequate, problematic, and weak. There was a positive and significant relationship between patients' anxiety and health literacy levels. Variables such as age, gender, marital status, education level, employment status, disease-related symptoms, a family history of cancer, and fear of colonoscopy influenced anxiety and health literacy. Based on these findings, we recommend that individuals' anxiety and health literacy status be determined before a colonoscopy procedure to improve gastroenterology nurses' management of these patients.

Outcomes of Conservative Indication Criteria for First-Line Treatment in Chronic Lymphocytic Leukemia: Insights from the Brazilian Registry of CLL

Introduction: Chronic lymphocytic leukemia (CLL) exhibits diverse treatment requirements, with some patients receiving immediate treatment while others remain under observation. In 2008, the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) established criteria for treatment indications, widely adopted in clinical practice and trials. The Brazilian Group of CLL (BGCLL) has been evaluating a more conservative approach to treatment indication performed in multiple centers, which avoids predefined cutoff levels for cytopenias and refrains from considering progressive lymphocytosis, extranodal involvement, or disease-related symptoms as isolated criteria. However, the safety and potential different outcomes of this conservative approach compared to the strict IWCLL criteria remain uncertain. Objective: This study aims to compare the outcomes of CLL patients without indication for treatment according to the BGCLL criteria, who were either treated or not based on the center's decision. Methods: We conducted a retrospective analysis of CLL patients enrolled in the Brazilian Registry of CLL, observed between January 2009 and March 2023, meeting the minimum data availability criteria for analysis and following IWCLL inclusion guidelines. Results: A total of 2396 patients from 41 centers were included. Among them, 1313 patients (55%) met the IWCLL criteria for treatment indication, while only 558 patients (23%) fulfilled the more conservative BGCLL indication. Of the 1240 untreated patients, 247 (20%) had a treatment indication based on IWCLL guidelines. Common indications for treatment initiation included cytopenias in 159 patients (64%), disease-related constitutional symptoms in 41 patients (17%), and symptomatic lymphadenopathy in 22 patients (9%). Non-treatment despite having an indication was attributed to BGCLL's more conservative criteria in 67% of cases, severe comorbidities in 6%, and death during follow-up in 27%. Among the 1156 treated patients, 90 patients (8%) received treatment despite lacking a treatment indication according to the IWCLL criteria. According to BGCLL's conservative criteria, 600 (48%) treated patients did not have a treatment indication. After a median follow-up of 58 months (range: 3-506), the overall survival (OS) was 70% at 8 years. Among patients without an indication for treatment according to BGCLL's conservative criteria, OS was significantly worse in treated patients (79%) compared to untreated patients (64%, P<0.0001, figure 1). Conclusion: These real-world data demonstrate that a conservative approach in indicating first-line treatment for CLL is safe and associated with improved survival, possibly by mitigating toxicities and treatment-related complications such as clonal selection. Furthermore, this strategy may conserve resources, enhancing drug accessibility for a larger number of patients in clear need of treatment, particularly in low-income countries.

Patient-Reported Improvements in Fatigue and Health-Related Quality of Life in the Phase 3 Studies Apply-PNH and Appoint-PNH Evaluating the Use of Iptacopan in C5 Inhibitor-Treated and Treatment-Naïve Patients with Paroxysmal Nocturnal Hemoglobinuria

Introduction: Iptacopan is a first-in-class, oral, selective complement factor B inhibitor that recently demonstrated efficacy and safety as monotherapy in both C5 inhibitor-treated (APPLY-PNH [NCT04558918], Peffault de Latour et al) and treatment-naïve (APPOINT-PNH [NCT04820530], Risitano et al) patients with paroxysmal nocturnal hemoglobinuria (PNH). The primary results of active-comparator controlled APPLY-PNH and single-arm APPOINT-PNH have been reported, showing clinically meaningful increases in hemoglobin levels while controlling intravascular hemolysis and preventing extravascular hemolysis. As patient-perceived benefits of therapies are increasingly important, we present here additional results of the patient-reported outcomes measures (PROMs) including responder analyses of changes from baseline in these two studies based on meaningful within-patient thresholds. Methods: The PROMs included an assessment of fatigue (FACIT-Fatigue) as the basis of a secondary endpoint, a health-related quality of life questionnaire (EORTC QLQ-C30), and a Patient Global Impression of Severity (PGIS) of Fatigue. Both studies analyzed change from baseline in PROMs between Day 1 and Day 168. In APPLY-PNH, another focus was on comparing treatments on the average of model-derived estimates for visits between Day 126 and Day 168. While 5 points on the FACIT-Fatigue was prespecified in the protocol, anchor-based meaningful within-patient change analyses utilizing the PGIS as the anchor determined the range for the magnitude of meaningful change for the FACIT-Fatigue to be 7.5 to 9.5 points (derived from APPLY-PNH); 9 points within the upper segment of the range was chosen as the threshold value used in this analysis. Analyses of the EORTC QLQ C-30 focused on the Physical and Role Functioning subscales and symptoms subscales evaluating Fatigue and Dyspnea. Responder analysis thresholds were determined for all 4 subscales using a combination of anchors including PGIS to determine meaningful change thresholds for each subscale. The ranges and threshold choices were based on the assessment of empirical cumulative distribution function (eCDF) of the scores by scale levels of the anchor and used the visit median values as representative levels to determine the range supporting threshold choices. Results: Ninety-five patients were from APPLY-PNH, of whom 62 received iptacopan and 33 received anti-C5 treatment, and 40 patients were from APPOINT-PNH. In APPLY-PNH, responder analysis showed that more patients in the iptacopan group achieved the threshold of ≥9 points compared with the anti-C5 group (51% vs 11%) ( Table 1). The strength of this result was confirmed by a non-parametric Mann-Whitney test with P values ≤0.0039. In APPOINT-PNH, 56% (95% CI, 43-68) achieved the threshold of ≥9 points and approximately half reached a higher threshold of 11 points ( Table 1). Analyses of EORTC QLQ-C30 further corroborated the results for both trials. Responder analyses in APPLY-PNH of the four subscales using internally derived thresholds showed average proportions of responders in the iptacopan group 39% to 49% and in the anti-C5 group ranging from 9% to 20% ( Table 2). The strength of these results was confirmed by a non-parametric assessment of cumulative distribution functions and Mann-Whitney with P values ≤0.0088. In APPOINT-PNH, the estimated average proportions of responders for EORTC QLQ C30 ranged from 41% to 55% ( Table 2). Conclusion: Both anti-C5-experienced and treatment-naïve patients receiving iptacopan exhibited clinically meaningful improvements in fatigue, health-related quality of life, and disease-related symptoms as measured by predetermined meaningful thresholds of response in FACIT-Fatigue and EORTC QLQ-C30. Together with previous presented primary efficacy data from APPLY-PNH and APPOINT-PNH, these results indicate that iptacopan not only results in clinically meaningful improvements in markers of disease control but provides meaningful improvements in aspects that are important to patients (ie, fatigue and other aspects of health-related quality of life, such as physical functioning and role functioning).

Elenestinib, an Investigational, Next Generation KIT D816V Inhibitor, Reduces Mast Cell Burden, Improves Symptoms, and Has a Favorable Safety Profile in Patients with Indolent Systemic Mastocytosis: Analysis of the Harbor Trial

Introduction Indolent systemic mastocytosis (ISM) is a rare clonal mast cell disease driven by the KIT D816V mutation in nearly all patients. Patients with ISM can present with debilitating acute and chronic cutaneous, gastrointestinal, neurocognitive, and systemic symptoms caused by the release of inflammatory mediators from abnormal mast cells. In some patients, symptoms are not adequately controlled with best supportive care (BSC) medications. Elenestinib (BLU-263) is a novel, investigational, oral, next-generation tyrosine kinase inhibitor that potently and selectively inhibits KIT D816V with limited central nervous system penetration and pharmacokinetics (PK) that support once daily dosing. HARBOR (NCT04910685) is a randomized, double-blind, placebo-controlled, phase 2/3 study assessing efficacy and safety of elenestinib in patients with ISM. Methods Eligible adult patients with ISM, confirmed following central review of bone marrow (BM) pathology, clinical, and laboratory findings per World Health Organization criteria and a moderate-to-severe symptom score based on minimum mean total symptom score (TSS) of the ISM-Symptom Assessment Form (ISM-SAF©2018), were stratified by baseline serum tryptase (<20 ng/mL vs ≥20 ng/mL) and randomly assigned 3:1 to elenestinib 25 mg, 50 mg, or 100 mg once daily + BSC (“elenestinib”) or placebo + BSC (“placebo”). The primary objective of Part 1 was to determine the recommended dose based on safety, PK, and pharmacodynamics. Secondary endpoints included changes in biomarkers of disease burden (serum tryptase, KIT D816V variant allele fraction [VAF], and BM mast cells) and ISM-SAF TSS. Three additional open-label PK groups enrolled patients at 50 mg, 75 mg, and 100 mg to further characterize PK and safety. Results As of data cutoff on July 3, 2023, a total of 122 patients with ISM have received their assigned treatment in Part 1 of the study; 39 were blinded and randomized to elenestinib or placebo, and 83 were treated with open-label elenestinib in the PK groups (21 patients at 50 mg, 34 patients at 75 mg, and 28 patients at 100 mg). Baseline demographics were similar to those reported for the general ISM population. After 12 weeks of therapy, symptom improvement was observed for all dose cohorts, and symptom reduction by TSS was greater for patients on elenestinib versus placebo in the blinded portion of Part 1. Patients receiving elenestinib at 25 mg, 50 mg, and 100 mg doses showed reduction (mean percent) from baseline for tryptase (-15.4%, -50.9%, and -68.4% vs 3.3%, respectively) and KIT D816VVAF (-37.5%, -70.3%, and -77.0% vs -2.5%, respectively) as compared to placebo. Similar reductions in TSS and disease-related biomarkers were observed in the open-label PK cohorts. After a median treatment duration of 35.3 weeks, elenestinib was well-tolerated at all dose levels. There were no treatment-related serious adverse events and no treatment-related adverse events that led to drug discontinuation. Conclusion Elenestinib at all tested doses demonstrated beneficial effects on disease-related symptoms and biomarkers of mast cell burden in this large and maturing cohort of patients with ISM with a moderate-to-severe symptom burden. Elenestinib was well tolerated across all dose levels with a promising early benefit-risk profile in ISM. These preliminary findings will inform dosing for the planned Part 2 of HARBOR, which will examine elenestinib versus placebo in a randomized, blinded, placebo-controlled setting.

Phase II Trial of Ibrutinib in Previously Untreated High-Risk Smoldering Mantle Cell Lymphoma

Background: Mantle cell lymphoma (MCL) patients usually require immediate therapy, however about 20% of newly diagnosed MCL patients can be initially observed. A subgroup of patients who are suitable for initial observation but exhibit high-risk features are of particular concern as they have a propensity to progress. We consider these patients as high-risk smoldering MCL (defined below). Generally, these patients are observed without systemic therapy for 18-24 months. We investigated the impact of single-agent ibrutinib on time to progression for these patients who would otherwise be observed. Methods: This is a single center, single arm, investigator-initiated phase 2 clinical trial (NCT03282396). High-risk smoldering MCL included one or more of the following criteria: non-blastoid/pleomorphic variant, Ki-67 of 15-30%, white blood cell count of 15-30 x 10^9/L, lymph nodes ≤5 cm, TP53 mutated or wild type, del17p, MYC positive, complex karyotype, presence of KMT2D, BIRC3, or ≥1 other somatic mutations, and were asymptomatic without any clinical indication to start systemic therapy. Major exclusion criteria included significant disease-related symptoms, blastoid/pleomorphic variants, Ki-67 >30%, bulky tumors >5 cm. Patients received ibrutinib 560 mg P.O. daily in 28-day cycles and continued until progression, transformation, drug intolerance, or up to 5 years. The primary endpoint was progression-free survival (PFS). Secondary endpoints were safety, response rate, and duration of response (DOR). Response was measured using the Lugano criteria. It is expected that the current trial will achieve a median PFS time of about 18 months, which would be an improvement over PFS reported on high-risk patients under a watch and wait approach. The median follow-up time was 23.4 months. Results: Twenty patients were enrolled (Table 1). The median age was 60.5 years (range 38-79). Most were male (n=15/20). At baseline, 13 patients (65%) had bone marrow involvement and 15 patients (75%) had gastrointestinal tract involvement. Seven patients (35%) had TP53 alterations. One patient was not evaluable for response due cessation of therapy after less than 1 cycle due to new onset atrial fibrillation. Among 19 evaluable patients, the best overall response rate was 94.7% (n=18/19). Of those who had a positive PET at baseline and were evaluable for PET response, 92.9% (n=13/14) achieved a PET complete response (CR). Of those with bone marrow involvement at baseline, 30.7% (n=4/13) achieved CR by flow cytometry. Of those with baseline gastrointestinal tract involvement, 33.3% (n=5/15) achieved histologically confirmed CR. The median number of cycles received was 16 (range 0-32). The median PFS and DOR were not reached. Seven patients discontinued therapy: atrial fibrillation (n=3), progressive disease (n=1), infection (n=1), lung cancer (n=1). The most frequent grade 3 toxicities were diarrhea (n=2, 10%), atrial fibrillation (n=1, 5%), infection (n=1, 5%), mucositis (n=1, 5%), and syncope (n=1, 5%). No grade 4 toxicities occurred. No deaths on study occurred. Conclusions: Ibrutinib demonstrated significant efficacy with manageable toxicities in previously untreated patients with high-risk smoldering MCL.

A Phase 2 Study of Fedratinib in Patients with MDS/MPN and Chronic Neutrophilic Leukemia

Introduction MDS/MPNs are clinically and molecularly complex diseases that exhibit proliferative symptoms and aggressive clinical courses. Evaluation of mutational patterns and gene expression profiles suggest these diseases should be viewed as a spectrum rather than distinct disease entities. Treatment options are limited and poorly defined as patients (pts) are often excluded from clinical trials. The JAK1/JAK2 inhibitor, ruxolitinib, has shown clinical benefit in pts with MDS/MPN and pts harboring CSF3R mutations. The experience of JAK2 inhibitors in myelofibrosis (MF) has shown that non-JAK2 kinase targets of JAK inhibitors may result in unique profiles of clinical benefit. Fedratinib is a JAK2 inhibitor approved for higher-risk MF. Compared to ruxolitinib, it has a broader kinase inhibition profile which may convey enhanced efficacy in high-risk, molecularly complex disease. Fedratinib potently inhibits FLT3 and BRD4 and potently suppresses c-Myc expression which may have biologic relevance in MDS/MPN. Study Design This is a phase 2, multi-institutional, investigator-initiated clinical trial (NCT05177211) assessing the efficacy of fedratinib in pts with atypical chronic myeloid leukemia (aCML), chronic neutrophilic leukemia (CNL), MDS/MPN-unclassifiable (MDS/MPN-U), and MDS/MPN-ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) per 2016 WHO classification. Inclusion criteria included splenomegaly (≥ 5 cm below left costal margin or ≥ 450 cc) and/or significant disease-related symptoms (MPN TSS ≥ 10). Pts with a platelet count < 35 x 10 9/L or peripheral/marrow blasts > 10% were excluded. There was no exclusion based on prior treatment. The primary endpoint of this ongoing study is overall response rate defined as complete or partial response or clinical benefit at 24 weeks per proposed MDS/MPN IWG response criteria. C-Myc (a potential biomarker for response) was stained in the bone marrow collected at baseline and week 24. C-Myc expression product was scored by multiplying % positive cells by intensity (0 = none, 1 = mild, 2 = moderate, 3 = marked). Fedratinib was given at a dose of 400 mg daily. Planned enrollment is 25 pts with an interim analysis completed after 9 pts are evaluable for efficacy. Results At time of data cut-off, 10 pts have been enrolled with a median follow-up of 5 months. Eight pts remain on treatment. Baseline demographics, genetic makeup, and treatment history are shown in table 1. Enrolled pts include 1 with aCML, 4 with CNL, 4 with MDS/MPN-RS-T, and 1 with MDS/MPN-U. Three or more mutations were present in 7 (70%) pts. Three of 5 (60%) evaluable pts responded at week 24. This included 3 (75%) symptom responses and 1 (20%) spleen response (1 pt with both). Six pts have completed 12 weeks of treatment with 1 spleen response and 2 symptoms responses (Figure 1). Among 6 pts with baseline splenomegaly who received 12 weeks of treatment, spleen volume decreased in 5 (83%) by an average of -23% (+5% to -71%). Among 5 pts with significant baseline symptom burden who received 12 weeks of treatment, 4 (80%) experienced an improvement in symptom burden by an average of -43% (range 0% to -76%). One pt who discontinued treatment prior to week 8 for reasons unrelated to disease or treatment was considered a spleen and symptom non-responder despite experiencing a 48% symptom improvement at week 4. At baseline, C-Myc expression was demonstrated by IHC staining in a median of 10% of cells (5-15%). Average baseline c-Myc expression product (% positive cells * staining intensity) was 26.5 (range 10-37.5). In pts with paired samples (n = 4), c-Myc expression product decreased in all cases by an average of 51% (25%-85%), p = 0.02. Ten pts were evaluable for safety. The most common AEs occurring in >2 pts were anemia, platelet count decrease, diarrhea, nausea, muscle cramp, and constipation. Grade ≥3 AEs were anemia (40%) and neutropenia (10%). There were no grade ≥ 3 non-hematologic AEs. Two pts discontinued study treatment: one due to disease progression after initial response and one due to pt decision unrelated to disease or treatment. Conclusion: Fedratinib demonstrates promising clinical efficacy in MDS/MPN and CNL pts with proliferative features. The safety profile is consistent with prior experience. Fedratinib's unique kinase inhibition profile may provide a mechanism for enhanced effectiveness in this pt population. Updated results will be presented at the meeting.

Patient-Reported Outcomes Among Patients with Triple-Class Refractory Multiple Myeloma in Real-World Clinical Practice: A Prospective, Multi-Site Observational Study

BACKGROUND Several studies have highlighted the poor outcomes observed among patients with relapsed/refractory multiple myeloma (MM), particularly those with triple-class refractory (TCR; refractory to at least one PI, one IMiD, and one anti-CD38 mAb) disease. The aim of this study was to describe the longitudinal changes in quality of life (QOL) and other patient-reported outcomes (PROs) among TCR MM patients in real-world clinical practice who initiate a new line-of-therapy. METHODS A prospective, multi-site observational study of patients with TCR MM was conducted through the Mayo Clinic system. Patients initiating a new post-TCR therapy (defined as the index date) were followed for a 12-month observation period during which PRO surveys were administered for the first 6 months. For patients initiating a CAR-T therapy, a survey assessment was conducted at apheresis, lymphodepletion chemotherapy, and every month after T-cell infusion until Month 6. All other patients received a survey assessment before index and then every month thereafter until Month 6. PRO measures included the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30; including the Global Health Score [GHS]), the EORTC Multiple Myeloma Questionnaire (QLQ-MY20; including the Disease Symptoms [DS] domain score), the EORTC QLQ for Chemotherapy-Induced Peripheral Neuropathy (CIPN20), the EuroQoL-5 Dimensions (EQ-5D), the Patient Global Impression of Severity (PGIS), and the Patient Global Impression of Change (PGIC). Patient surveys were supplemented with retrospective chart reviews conducted 3 months and 12 months following the index date to obtain clinical information. Descriptive data were reported at each timepoint separately for patients who received CAR-T and non-CAR-T index therapies. The study is ongoing and this abstract reflects all patient visit data as of April 2023. RESULTS N=55 patients (60% male, 96% White, mean age 66 years) were included in this interim analysis. The median time interval between becoming TCR and the index date was 3.9 months (interquartile range [IQR]: 1.7, 15.5). Most patients had an ECOG score of 0 or 1 (53% and 38%, respectively) and were R-ISS I or II (36% and 54%, respectively); 53% of patients had high-risk cytogenetics and 20% had extramedullary disease. The median (IQR) number of prior treatment lines was 4 (4.0, 5.5). N=24 patients initiated a CAR-T therapy as their index therapy (equally split between ide-cel and cilta-cel); the remaining N=31 patients predominantly initiated a treatment regimen containing an IMiD (52%), a PI (55%), an anti-CD38 antibody (13%), or an alkylating agent (36%). Among CAR-T patients, QOL and disease-related symptoms worsened from baseline through Month 2-3 (eg, mean GHS was 65.9 at apheresis, 64.9 at lymphodepletion, and 53.3 at Month 2 [higher scores indicate better QOL]; mean DS domain score from the QLQ-MY20 was 24.1 at apheresis, 23.4 at lymphodepletion, and 33.7 at Month 2 [higher scores indicate more symptoms]; see Table 1). These decrements were followed by improvement back to baseline levels and, in some cases, improvement above baseline levels (eg, GHS was 67.9 and 65.0 at Months 4 and 5, respectively; DS was 18.3 and 17.8 at Months 4 and 5), though few patients had sufficient follow up to analyze QOL at later timepoints. Based on the PGIC, 77.8% of patients reported being “a little better” or “much better” as early as Month 1, though this number declined over time. Among non-CAR-T patients, QOL largely plateaued (GHS was 62.2 at baseline and 58.3 at Month 6), though disease symptoms improved over time (DS was 28.6 at baseline and 24.5 at Month 6; pain was 42.3 at baseline and 29.2 at Month 6). Based on the PGIC, 34.7% of patients reported being “a little better” or “much better” at Month 1, which improved to 50% by Month 6. CONCLUSIONS In this interim analysis of an ongoing prospective observational study, QOL and symptom measures generally worsened over the first few months for CAR-T patients in the real-world though improved to baseline levels and beyond at later time points. Patients did, however, directly report improvement in their disease state as early as Month 1 based on the PGIC. Non-CART patients generally showed a QOL plateau with some modest improvement in disease symptoms which was also reflected in their self-reported assessment of disease state improvement based on the PGIC.

The Burden of Sickle Cell Disease on Children and Their Caregivers: Caregiver Reports of Children's Health-Related Quality of Life and School Experiences, Caregiver Burden, and Their Association with Frequency of Vaso-Occlusive Crises.

Children with sickle cell disease (SCD) experience a multiplex of disease-related symptoms and complications, including vaso-occlusive crises (VOCs), episodes characterized by extreme pain. A cross-sectional observational survey examined the health-related quality of life (HRQoL) and school experiences of children with SCD 2 months-11 years, burden experienced by their caregivers, and associations between these outcomes and VOC frequency. Caregivers (N=167) of children with SCD in the US completed the Infant-Toddler Quality of Life-Short Form 47 (ITQoL-SF47) for children 2 months-4 years, the Child Health Questionnaire-Parent Form 50 (CHQ-PF50) and PROMIS Pain Interference and Sleep Disturbance Parent Proxy short forms for children 5-11 years, and a study-specific survey of school experiences. Children with SCD 2 months-4 years had lower ITQoL-SF47 scores (ie, worse HRQoL, p<0.001) than a normative sample of children; across domains, differences ranged from 18.73-45.03 points and exceeded minimal important difference (MID) thresholds. Except for the behavior domain, children with SCD 5-11 years had lower scores on all CHQ-PF50 domains than the normative sample (p<0.001); differences ranged from 6.78-36.37 points and exceeded MID thresholds. Children with more frequent VOCs had lower HRQoL and worse school experiences than children with less frequent VOCs (p<0.05, except for behavior domains). The largest differences based on VOC frequency were observed for overall health and bodily pain/discomfort among children 2 months-4 years (differences=40.88 and 32.50 points, respectively), and bodily pain and role/social limitations due to physical health among children 5-11 years (differences=38.99 and 37.80, respectively). Caregivers of children with more frequent VOCs experienced greater burden than caregivers of children with less frequent VOCs, though specific areas of impact (eg, caregiver emotions, time) differed across child age groups. VOC frequency is negatively associated with HRQoL, highlighting the burden experienced by children with SCD and their caregivers.

Long-acting interferon: pioneering disease modification of myeloproliferative neoplasms.

Myeloproliferative neoplasms (MPNs) are clonal disorders of hematopoietic stem cells. The malignant clones produce cytokines that drive self-perpetuating inflammatory responses and tend to transform into more aggressive clones, leading to disease progression. The progression of MPNs follows a biological sequence from the early phases of malignancy, polycythemia vera, and essential thrombocythemia, to advanced myelofibrosis and leukemic transformation. To date, the treatment of MPNs has focused on preventing thrombosis by decreasing blood cell counts and relieving disease-related symptoms. However, interferon (IFN) has been used to treat MPNs because of its ability to attack cancer cells directly and modulate the immune system. IFN also has the potential to modulate diseases by inhibiting JAK2 mutations, and recent studies have demonstrated clinical and molecular improvements. Long-acting IFN is administered less frequently and has fewer adverse effects than conventional IFN. The current state of research on long-acting IFN in patients with MPNs is discussed, along with future directions.

The role of muscle degeneration and spinal balance in the pathophysiology of lumbar spinal stenosis: Study protocol of a translational approach combining in vivo biomechanical experiments with clinical and radiological parameters.

To describe a study protocol for investigating the functional association between posture, spinal balance, ambulatory biomechanics, paraspinal muscle fatigue, paraspinal muscle quality and symptoms in patients with symptomatic lumbar spinal stenosis (sLSS) before and 1-year after elective surgical intervention. Single-centre prospective, experimental, multimodal (clinical, biomechanical, radiological) study with three instances of data collection: baseline (study visit 1), 6-month follow-up (remote) and 1-year follow-up (study visit 2). Both study visits include an in vivo experiment aiming to elicit paraspinal muscle fatigue for postural assessment in a non-fatigued and fatigued state. At baseline and 1-year follow-up, 122 patients with sLSS will be assessed clinically, perform the back-performance scale assessment and complete several patient-reported outcome measure (PROMs) questionnaires regarding overall health, disease-related symptoms and kinesiophobia. Posture and biomechanical parameters (joint kinematics, kinetics, surface electromyography, back curvature) will be recorded using an optoelectronic system and retroreflective markers during different tasks including overground walking and movement assessments before and after a modified Biering-Sørensen test, used to elicit paraspinal muscle fatigue. Measurements of muscle size and quality and the severity of spinal stenosis will be obtained using magnetic resonance imaging (MRI) and sagittal postural alignment data from EOS radiographies. After each study visit, physical activity level will be assessed during 9 days using a wrist-worn activity monitor. In addition, physical activity level and PROMs will be assessed remotely at 6-month follow-up. The multimodal set of data obtained using the study protocol described in this paper will help to expand our current knowledge on the pathophysiology, biomechanics, and treatment outcome of degenerative sLSS. The results of this study may contribute to defining and/or altering patient treatment norms, surgery indication criteria and post-surgery rehabilitation schedules. The protocol was approved by the regional ethics committee and has been registered at clinicaltrials.gov (NCT05523388).

Identifying Potential Lyme Disease Cases Using Self-Reported Worldwide Tweets: Deep Learning Modeling Approach Enhanced With Sentimental Words Through Emojis.

Lyme disease is among the most reported tick-borne diseases worldwide, making it a major ongoing public health concern. An effective Lyme disease case reporting system depends on timely diagnosis and reporting by health care professionals, and accurate laboratory testing and interpretation for clinical diagnosis validation. A lack of these can lead to delayed diagnosis and treatment, which can exacerbate the severity of Lyme disease symptoms. Therefore, there is a need to improve the monitoring of Lyme disease by using other data sources, such as web-based data. We analyzed global Twitter data to understand its potential and limitations as a tool for Lyme disease surveillance. We propose a transformer-based classification system to identify potential Lyme disease cases using self-reported tweets. Our initial sample included 20,000 tweets collected worldwide from a database of over 1.3 million Lyme disease tweets. After preprocessing and geolocating tweets, tweets in a subset of the initial sample were manually labeled as potential Lyme disease cases or non-Lyme disease cases using carefully selected keywords. Emojis were converted to sentiment words, which were then replaced in the tweets. This labeled tweet set was used for the training, validation, and performance testing of DistilBERT (distilled version of BERT [Bidirectional Encoder Representations from Transformers]), ALBERT (A Lite BERT), and BERTweet (BERT for English Tweets) classifiers. The empirical results showed that BERTweet was the best classifier among all evaluated models (average F1-score of 89.3%, classification accuracy of 90.0%, and precision of 97.1%). However, for recall, term frequency-inverse document frequency and k-nearest neighbors performed better (93.2% and 82.6%, respectively). On using emojis to enrich the tweet embeddings, BERTweet had an increased recall (8% increase), DistilBERT had an increased F1-score of 93.8% (4% increase) and classification accuracy of 94.1% (4% increase), and ALBERT had an increased F1-score of 93.1% (5% increase) and classification accuracy of 93.9% (5% increase). The general awareness of Lyme disease was high in the United States, the United Kingdom, Australia, and Canada, with self-reported potential cases of Lyme disease from these countries accounting for around 50% (9939/20,000) of the collected English-language tweets, whereas Lyme disease-related tweets were rare in countries from Africa and Asia. The most reported Lyme disease-related symptoms in the data were rash, fatigue, fever, and arthritis, while symptoms, such as lymphadenopathy, palpitations, swollen lymph nodes, neck stiffness, and arrythmia, were uncommon, in accordance with Lyme disease symptom frequency. The study highlights the robustness of BERTweet and DistilBERT as classifiers for potential cases of Lyme disease from self-reported data. The results demonstrated that emojis are effective for enrichment, thereby improving the accuracy of tweet embeddings and the performance of classifiers. Specifically, emojis reflecting sadness, empathy, and encouragement can reduce false negatives.

A simplified prognostic score for T-cell large granular lymphocyte leukaemia

Background T-cell large granular lymphocyte leukaemia (T-LGLL) generally has a favourable prognosis, but a small proportion of patients are facing a relatively short survival time. This study aimed to identify clinical factors associated with survival in patients with T-LGLL and develop a predictive model for guiding therapeutic decision-making. Materials and Methods We conducted a retrospective study on 120 patients with T-LGLL. Lasso regression was performed for feature selection followed by univariate and multivariate Cox regression analysis. A decision tree algorithm was employed to construct a model for predicting overall survival (OS) in T-LGLL. Results The median age of diagnosis for the entire cohort was 59 years, and 76.7% of patients reported disease-related symptoms. After a median follow-up of 75 months, the median OS was not reached. The 5-year OS rate was 82.2% and the 10-year OS rate was 63.8%. Multivariate analysis revealed that an Eastern Cooperative Oncology Group performance status over two and a platelet count below 100 × 109/L were independently associated with worse OS, leading to the development of a simplified decision tree model. The model’s performance was adequate when internally validated. The median OS of the high- and intermediate-risk- risk groups was 43 and 100 months respectively, whereas the median OS of the low-risk group was not reached. Furthermore, we found that immunosuppressive agent-based conventional treatment was unsatisfactory for our high-risk patients. Conclusions Our model is an easily applicable clinical scoring system for predicting OS in patients with T-LGLL. However, external validation is essential before implementing it widely.

OR23-05 Log-term Efficacy And Safety Of Transcon PTH In Adults With Hypoparathyroidism: 52-week Results From The Open-label Extension Of The Phase 3 Pathway Trial

OR23-05 Log-term Efficacy And Safety Of Transcon PTH In Adults With Hypoparathyroidism: 52-week Results From The Open-label Extension Of The Phase 3 Pathway Trial

An online and telehealth intervention for women diagnosed with gynecological cancer during the COVID-19 pandemic: The Journey Ahead pilot and feasibility trial

Abstract Background: Women diagnosed with gynecological cancer suffer from disease-related and treatment-related symptoms that can result in diminished quality of life and persistent distress. There are few evidence-based treatments to mitigate distress for these survivors. Objective: The aim of this study was to evaluate the feasibility, acceptability, and preliminary effects of Journey Ahead, a blended online and telehealth coaching intervention adapted from the in-person Coping and Communication Intervention. Methods: Fourteen women diagnosed and treated for gynecological cancer completed a baseline survey and were enrolled in Journey Ahead, which consisted of eight online modules and five telehealth coaching calls, and then completed a follow-up survey and treatment evaluation. Results: Acceptance rates (27.5%) and follow-up survey completion (57.1%) were lower than expected. Eighty-six percent of participants logged into the online program, and 64.2% completed it. Eighty-three percent of participants completed four or five of the telehealth sessions, and 35.7% attended one session or did not attend any of the telehealth sessions. The results indicated that this intervention reduced depressive symptoms and cancer-related distress and increased emotional well-being, emotional expression, acceptance, psychological flexibility, and coping efficacy. Conclusions: The results highlight the challenges of recruiting during the COVID-19 pandemic and the importance of collecting detailed information from study participants about how to engage them in fully remote interventions. Overall, this single-arm pilot and feasibility study demonstrated satisfactory feasibility, excellent acceptability, and a promising preliminary impact on psychological outcomes.

The Impact of Palliative Chemotherapy on the Survival of Patients With Metastatic Colorectal Cancer in Jordan.

Background In Jordan, managing metastatic colorectal cancer (mCRC) is particularly complex, considering limited resources, access to advanced therapies, and unique patient demographics. Palliative chemotherapy, an approach aimed at relieving symptoms and improving the quality of life in patients with advanced cancer, including mCRC, has gained attention as a treatment strategy. While palliative chemotherapy may not aim for complete cancer eradication, it can extend survival, manage disease-related symptoms, and enhance the patient's overall well-being. However, deciding to pursue palliative chemotherapy for mCRC patients involves individual patient characteristics, performance status, disease aggressiveness, potential treatment-related adverse effects, and available healthcare resources. Given the need for region-specific insights into treatment outcomes, the proposed study seeks to investigate the impact of palliative chemotherapy on overall survival (OS), specifically within Jordan's healthcare landscape. Our study aims to showcase palliative chemotherapy's effectiveness on OS in first-line settings. Materials and methods This study is a retrospective analysis conducted at the Military Cancer Center (MCAC) in Jordan. It includes 73 patients diagnosed with mCRC between January 1, 2018, and January 1, 2020. Data were obtained from electronic medical records, and patients were monitored until June 10, 2023. Various patient characteristics were analyzed, including age, sex, primary tumor site, metastatic site,and treatment options for mCRC. The study evaluated the effectiveness of palliative chemotherapy in improving survival rates compared to BSC. Result We conducted a study with 73 participants, whose mean age was 60.37 ±13.5 years and a median of 63. Of these patients, 51 (69.9%) were male, and 22 (30.1%) were female. The primary site of the tumor was located on the left side in 32 patients (43.9%), on the right side in 26 patients (35.6%), and rectal cancer in 15 patients (20.5%). The most common site of the tumor was the sigmoid (17 patients, 23.3%). The liver was the most common site of metastasis (52 patients, 71.2%). Of the patients, 47 (64.4%) received palliative chemotherapy, while 26 (35.6%) were kept on best supportive care (BSC). Of those who received chemotherapy, FOLFIRI was administered to 32 patients (43.8%) and FOLFOX to 15 patients (20.5%). Based on the Kaplan-Meier curve, palliative chemotherapy patients had a significantly longer OS than those who only received BSC. Patients with palliative chemotherapy had a median OS of 12.4 months, while those who only had BSC survived for 5.3 months. The HR was 0.36 with a 95% confidence interval of 0.2-0.62, and the P-value was less than 0.001. Conclusion This study shows that palliative chemotherapy offers a notable advantage and a significant survival benefit compared to BSC.

Moving toward disease modification in polycythemia vera

AbstractPolycythemia vera (PV) belongs to the BCR-ABL1–negative myeloproliferative neoplasms and is characterized by activating mutations in JAK2 and clinically presents with erythrocytosis, variable degrees of systemic and vasomotor symptoms, and an increased risk of both thromboembolic events and progression to myelofibrosis and acute myeloid leukemia (AML). Treatment selection is based on a patient’s age and a history of thrombosis in patients with low-risk PV treated with therapeutic phlebotomy and aspirin alone, whereas cytoreductive therapy with either hydroxyurea or interferon alfa (IFN-α) is added for high-risk disease. However, other disease features such as significant disease-related symptoms and splenomegaly, concurrent thrombocytosis and leukocytosis, or intolerance of phlebotomy can constitute an indication for cytoreductive therapy in patients with otherwise low-risk disease. Additionally, recent studies demonstrating the safety and efficacy (ie, reduction in phlebotomy requirements and molecular responses) of ropegylated IFN-α2b support its use for patients with low-risk PV. Additionally, emerging data suggest that early treatment is associated with higher rates of molecular responses, which might eventually enable time-limited therapy. Nonetheless, longer follow-up is needed to assess whether molecular responses associate with clinically meaningful outcome measures such as thrombosis and progression to myelofibrosis or AML. In this article, we provide an overview of the current and evolving treatment landscape of PV and outline our vision for a patient-centered, phlebotomy-free, treatment approach using time-limited, disease-modifying treatment modalities early in the disease course, which could ultimately affect the natural history of the disease.

Can a modified ketogenic diet be a nutritional strategy for patients with McArdle disease? Results from a randomized, single-blind, placebo-controlled, cross-over study

McArdle disease is caused by myophosphorylase deficiency leading to blocked glycogenolysis in skeletal muscle. Consequently, individuals with McArdle disease have intolerance to physical activity, muscle fatigue, and pain. These symptoms vary according to the availability of alternative fuels for muscle contraction. In theory, a modified ketogenic diet (mKD) can provide alternative fuels in the form of ketone bodies and potentially boost fat oxidation. This randomized, single-blind, placebo-controlled, cross-over study aimed to investigate if a mKD improves exercise capacity in individuals with McArdle disease. Participants were randomized to follow a mKD (75-80% fat, 15% protein, 5-10% carbohydrates) or placebo diet (PD) first for three weeks, followed by a wash-out period, and then the opposite diet. The primary outcome was change in heart rate during constant-load cycling. Secondary outcomes included change in plasma metabolites, perceived exertion, indirect calorimetry measures, maximal exercise capacity, and patient-reported outcomes. Fifteen out of 20 patients with genetically verified McArdle disease completed all study visits, and 14 were included in the data analyses. We found that the mKD induced a metabolic shift towards increased fat oxidation (∼60% increase), and a 19-fold increase in plasma β-hydroxybutyrate (p<0.05). The mKD did not improve heart rate responses during constant-load cycling but did improve patient-reported outcomes and maximal exercise capacity (∼20% increase) compared to the PD. The mKD did not alleviate all McArdle disease-related symptoms but did induce some positive changes. To date, no satisfactory treatment options exist other than exercise training. To that end, a mKD can be a possible nutritional strategy for some individuals with McArdle disease who are motivated to undertake a restrictive diet. clinical trials.gov: NCT04044508.

Cardiac rehabilitation engagement and associated factors among heart failure patients: a cross-sectional study

BackgroundChronic Heart Failure (CHF) still affects millions of people worldwide despite great advances in therapeutic approaches in the cardiovascular field. Cardiac rehabilitation (CR) is known to improve disease-related symptoms, quality of life and clinical outcomes, yet implementation is suboptimal, a frequently low engagement in rehabilitation programs has been found globally.ObjectiveTo quantify diverse CR-engaged processes and elucidate associated factors of the various levels of CR engagement in CHF patients.MethodsDischarged patients admitted from cardiology departments between May 2022 to July 2022 were enrolled by mobile phone text messaging, CHF patients from same department between August 2022 to December 2022 were enrolled by face-to-face. Individuals who met the inclusion criteria filled the questionnaires, including the generalized anxiety disorders scale, patient health questionnaire, cardiac rehabilitation inventory, patient activation measure, Tampa scale for kinesiophobia heart, social frailty, Patient Health Engagement Scale (PHE-s®). We obtained sociodemographic characteristics and clinical data from medical records. Chi-square tests and multivariable logistic regression analyses were performed to examine the factors associated with CR engagement phases.ResultsA total of 684 patients were included in the study. 52.49% patients were in the Adhesion phase. At the multivariate level, compared with the blackout phase process anxiety, monthly income (RMB yuan) equal to or more than 5,000 were the most important factor impacting CHF patients CR engagement. Compared with the Blackout phase, regular exercise or not, severe depression, previous cardiac-related hospitalizations 1 or 2 times, Age influenced patient CR engagement in the Arousal phase. Besides, compared with the Blackout phase, outcome anxiety and activation level were independent factors in the Eudaimonic Project phase.ConclusionThis study characterized CR engagement, and explored demographic, medical, and psychological factors—with the most important being process anxiety, monthly income, patient activation, severe depression, and previous cardiac-related hospitalizations. The associated factors of CR engagement were not identical among different phases. Our findings suggested that factors could potentially be targeted in clinical practice to identify low CR engagement patients, and strategies implemented to strengthen or overcome these associations to address low CR engagement in CHF patients.

JS01.5.A PHASE 2 TRIAL OF CARBOPLATIN AND BEVACIZUMAB FOR RECURRENT ADULT EPENDYMOMA. A CERN STUDY

Abstract BACKGROUND Most adults with ependymoma undergo tumor resection at the time of diagnosis, which may be followed by radiation. At recurrence, re-resection and/or (re)-irradiation may be given, however, there are few established chemotherapy treatments. A previous retrospective report of 8 patients treated with carboplatin and bevacizumab showed a high response rate with 6 patients demonstrating an imaging response (Green, Neurology 2009). We sought to further investigate this regimen with a prospective trial. MATERIAL AND METHODS We performed a prospective phase 2 study in the CERN Adult Clinical Trials Network. Adult patients with recurrent or progressive ependymoma were enrolled to receive carboplatin (AUC =4-5) every 4 weeks for up to 6 cycles and bevacizumab at 10mg/kg every 2 weeks for one year, with the option to continue until progression or toxicity. The primary endpoint was 12-month PFS rate and &amp;gt;50% defined efficacy. Serial symptom burden measurement at baseline and at the time of disease evaluation using MD Anderson Symptom Inventory-brain tumor (MDASI-BT) or MDASI-Spine patient-reported outcomes (PROs) were used to evaluate the clinical impact of PFS. RESULTS A total of 22 patients with median age of 45 years were accrued and treated; 11 were women. WHO grade was 3 in 13 patients and grade 2 in 9 patients (3 with myxopapillary ependymoma) Ten patients had only spinal cord disease, 3 had both spinal cord and brain involvement and 9 patients had brain involvement alone (6 supratentorial, 3 infratentorial). Previous treatments included radiotherapy in all 22 patients and alkylating chemotherapy in 9 patients. Treatment was well tolerated with expected myelotoxicities and hypertension. The Kaplan-Meier calculated 12-Month PFS rate was 76.4% (95%CI 52.2%, 89.4%), median PFS = 18 months (95%CI 12.2, +∞). There were 2 partial responses (9.1%). Brain tumor responders (objective response or stable disease) showed reduction while non-responders had an increase in both neurologic and cognitive symptoms but similar report of other symptoms. Spine tumor responders and non-responders both showed worsening disease-related symptoms; autonomic symptoms worsened in responders. Activity related interference worsened for all patients. CONCLUSION This treatment regimen was safe and met the primary efficacy endpoint of 12-month PFS rate. The improvement in disease-related symptoms in brain tumor patients supports that the achieved disease stability was clinically meaningful, but the increased activity-related interference suggests that treatment-associated symptoms may impact work, general activity, and walking ability during treatment. Improvements in spine tumor disease-associated symptoms were not seen. A confirmatory trial is warranted to further investigate the findings and to determine if there are differences in response amongst ependymoma subtypes and tumor location.