Relapse Status Research Articles

Survival outcomes of patients with diffuse large B-cell lymphoma undergoing autologous stem cell transplantation in Germany: real-world evidence from an administrative database between 2010 and 2019.

Limited real-world evidence is available for patients with diffuse large B-cell lymphoma (DLBCL) who received an autologous stem cell transplantation (ASCT) in Germany. This study aims to describe the real-world survival outcomes of patients with DLBCL who received ASCT in Germany after diagnosis. This study is a retrospective database analysis covering the period between 2010 and 2019. Unadjusted overall survival (OS) was plotted using the Kaplan-Meier estimator for the overall population and stratified by relapse status. A Cox regression was run to identify factors that influence OS. A total of 112 patients received an ASCT, with the average time from first-line treatment to ASCT being 11.7 months. The median OS estimated by Kaplan-Meier was 83.4 months for the entire cohort. The only variable that significantly reduced the OS was the presence of subsequent treatment after ASCT in a time-dependent model. OS after ASCT for DLBCL patients in Germany is higher than previously reported and may still be considered a valid option for carefully selected patients with relapsed/refractory DLBCL.

Clinical features of gastrointestinal symptoms in women with recurrent course of deep infiltrative endometriosis

Background. Endometriosis is a chronic multifactorial disease that affects more than 170 million women of reproductive age worldwide, causing pelvic pain syndrome, dyspareunia, and symptoms of gastrointestinal dyspepsia, thereby having a negative impact on the psycho-emotional state of patients. Despite a wide range of medical and surgical treatments, the relapse rate reaches 50%, which is a global economic and social problem.The purpose of the study. To determine the spectrum of clinical features of the gastrointestinal tract in women with recurrent deep infiltrative endometriosis.Materials and methods. The study included 113 patients of reproductive age who underwent surgical treatment of common forms of external genital endometriosis. The main group consisted of 32 patients who underwent repeated surgical treatment due to relapse of deep infiltrative endometriosis, the comparison group — 51 patients without relapse of the disease one year after the primary operation, the control group — 30 patients of reproductive age who did not suffer from external genital endometriosis. An analysis of the somatic anamnesis was carried out, as well as questionnaire data on pelvic pain on a visual analogue scale (VAS) and functional bowel disorders in patients with deep infiltrating endometriosis, depending on the status of relapse of the disease.Results and discussion. Patients of the main group suffered significantly more often from functional diseases of the gastrointestinal tract (71.9% (23/32) versus 51.3% (26/51) in the comparison group; p = 0.006, the spectrum of which was represented by chronic gastritis and irritable bowel syndrome. In the main group, the clinical manifestations of gastrointestinal dyspepsia before surgical treatment correspond to a moderately severe degree of 17.706 (4.601) points. A significantly higher initial level of functional intestinal disorders was established during subjective assessment in the main observation group: 17.706 (4.601) points versus 10.66 (3.61) points in the comparison group; p=0.001. In women of the main observation group, one month after surgical treatment, there was a significant decrease in subjective assessment of the severity of functional intestinal disorders (from 17.71 (4.60) points to 9.86 (4.73) points; p = 0.001). The integral VAS pain score in the main group was 6.65 (1.53) points, which is significantly higher than in patients in the comparison group without relapse of the disease.Conclusions. The identified clinical and anamnestic predictors of the recurrent course of deep infiltrative endometriosis will allow us to formulate a personalized approach at the pre- and postoperative stage, aimed at preventing relapse of the disease, which will directly improve the psycho-emotional state and quality of life of women.

Association of Disease-Modifying Treatment With Outcome in Patients With Relapsing Multiple Sclerosis and Isolated MRI Activity.

Isolated value of MRI metrics in relapsing multiple sclerosis (RMS) as a surrogate marker of response to disease-modifying treatment (DMT) and, thus, as decision criteria for DMT escalation in the absence of clinical signs of disease activity is still a matter of debate. The aim of this study was to investigate whether DMT escalation based on isolated MRI activity affects clinical outcome. Combining data from 5 MS centers in Austria and Switzerland, we included patients with RMS aged at least 18 years who (1) had initiated first-line, low-to-moderate-efficacy DMT (interferon β, glatiramer acetate, teriflunomide, or dimethyl fumarate) continued for ≥12 months, (2) were clinically stable (no relapses or disability progression) on DMT for 12 months, (3) had MRI at baseline and after 12 months on DMT, and (4) had available clinical follow-up for ≥2 years after the second MRI. The primary endpoint was occurrence of relapse during follow-up. The number of new T2 lesions (T2L) and DMT strategy (continuing low-/moderate-efficacy DMT vs escalating DMT) were used as covariates in regression analyses. A total of 131 patients with RMS, median age of 36 (25th-75th percentiles: 29-43) years, 73% women, were included and observed over a median period of 6 (5-9) years after second MRI. Sixty-two (47%) patients had relapse. Patients who continued first-line DMT had a 3-fold increased risk of relapse given 2 new T2L (hazard ratio [HR] 3.2, lower limit [LL] of 95% CI: 1.5) and a 4-fold increased risk given ≥3 new T2L (HR 4.0, LL-CI: 2.1). Escalation of DMT lowered the risk of relapse in patients with 2 new T2L by approximately 80% (HR 0.2, upper limit [UL] of 95% CI: 1.3) and with ≥3 new T2L by 70% (HR 0.3, UL-CI: 0.8). In case of only 1 new T2L, the increased risk of relapse and the treatment effect did not reach statistical significance of 5%. In our real-world cohort of patients clinically stable under low-to-moderate-efficacy DMT, escalation of DMT based on isolated MRI activity decreased risk of further relapse when at least 2 new T2L had occurred. This study provides Class III evidence that clinically stable patients with MS on low-/moderate-efficacy DMT with ≥3 new T2L on MRI who escalate DMT have a reduced risk of relapse and Expanded Disability Status Scale progression.

Machine learning-based evaluation of prognostic factors for mortality and relapse in patients with acute lymphoblastic leukemia: a comparative simulation study

BackgroundPredicting mortality and relapse in children with acute lymphoblastic leukemia (ALL) is crucial for effective treatment and follow-up management. ALL is a common and deadly childhood cancer that often relapses after remission. In this study, we aimed to apply and evaluate machine learning-based models for predicting mortality and relapse in pediatric ALL patients.MethodsThis retrospective cohort study was conducted on 161 children aged less than 16 years with ALL. Survival status (dead/alive) and patient experience of relapse (yes/no) were considered as the outcome variables. Ten machine learning (ML) algorithms were used to predict mortality and relapse. The performance of the algorithms was evaluated by cross-validation and reported as mean sensitivity, specificity, accuracy and area under the curve (AUC). Finally, prognostic factors were identified based on the best algorithms.ResultsThe mean accuracy of the ML algorithms for prediction of patient mortality ranged from 64 to 74% and for prediction of relapse, it varied from 64 to 84% on test data sets. The mean AUC of the ML algorithms for mortality and relapse was above 64%. The most important prognostic factors for predicting both mortality and relapse were identified as age at diagnosis, hemoglobin and platelets. In addition, significant prognostic factors for predicting mortality included clinical side effects such as splenomegaly, hepatomegaly and lymphadenopathy.ConclusionsOur results showed that artificial neural networks and bagging algorithms outperformed other algorithms in predicting mortality, while boosting and random forest algorithms excelled in predicting relapse in ALL patients across all criteria. These results offer significant clinical insights into the prognostic factors for children with ALL, which can inform treatment decisions and improve patient outcomes.

A - 22 Effects of Gender on the Relationship between Coping Styles and Executive Functioning in Alcohol Use Disorders

Abstract Objective Executive functioning (EF) and coping styles are important factors likely to influence risk and resilience to relapse following Alcohol Use Disorder (AUD) treatment. This study aims to evaluate EF and coping as independent predictors of relapse and the interplay between these two constructs by treatment outcome group and gender differences. Methods 23 females and 59 males in AUD residential treatment programs completed self-report questionnaires, a neuropsychological battery, and were followed for six months to determine treatment outcome. A logistic regression analysis was performed to evaluate coping (Brief COPE Inventory) and EF (Delis-Kaplan Executive Function System, Color-Word Interference Test, CWIT; inhibition and switching conditions) variables as predictors of relapse status. Significant predictors were evaluated by group status and gender to understand the association between coping and EF using Pearson correlation within each group. Results Gender (B = 8.6, p = 0.032), two coping (self-distraction (B = 2.3, p = 0.051) and humor (B = 1.9, p = 0.051)) and two EF (CWIT inhibition (B = 0.5, p = 0.007) and CWIT switching (B = 1.9, p = 0.006)) variables resulted in 85.4% overall classification accuracy. Correlations between these coping and EF, when evaluated by treatment group and gender, revealed significant gender-specific associations only among the relapse groups: self-distraction and CWIT inhibition (r = 0.379) in females and humor and CWIT inhibition (r = 0.242) in males. Conclusion Overall, EF and coping styles have independent predictive value for determining relapse risk in individuals with AUD. Poor EF skills may inhibit an individual’s ability to engage in appropriate coping during times of emotional distress. Understanding gender differences in relation to these dynamic relationships is essential for creating supportive and effective psychosocial interventions.

Approach to cases diagnosed with mesenteric panniculitis

Objective: In this study, it was aimed to report the diagnosis, treatment and follow-up results of patients who came to the hospital with complaints of abdominal pain and were diagnosed with Mesenteric Panniculitis (MP) by Abdominal Computed Tomography (ACT). Method: 32 patients diagnosed with MP by ACT were examined retrospectively. The patients' age, gender, admission leukocyte count, CRP values, comorbidities, medications prescribed at discharge, and relapse status were evaluated. Results: Of the 32 patients included in the study, 11 were male (34.4%), 21 were female (65.6%), and they had a mean age of 58.75±12.31 years. The average leukocyte value at first admission was 8240±2530 /mm³, CRP average 24.93±47.39 mg/L, neutrophil percentage was not above 80% in any patient. No patients were hospitalized. Recurrence was occurred in 2 (6.25%) patients (after 6 months and 28 months). No malignancy were during follow-up. Conclusion: MP was diagnosed with ACT. No biopsy was required for diagnosis. Medical treatment was sufficient, no surgical procedure was performed on the patients.

Assessing the impact of aprepitant on response to dose-intensive cyclophosphamide, etoposide, and cisplatin (DICEP).

Despite evidence demonstrating the effectiveness of aprepitant for chemotherapy-induced nausea and vomiting (CINV), its use in stem cell transplant settings across Canada is not standard. While pharmacokinetic data exists, the clinical significance of cytochrome P450 3A4 (CYP 3A4) inhibition of cyclophosphamide by aprepitant is unclear. Reduced activation of cyclophosphamide may reduce the effectiveness of dose-intensive cyclophosphamide, etoposide, and cisplatin (DICEP). To compare response rates to DICEP in patients with Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL) in the presence and absence of aprepitant. A retrospective review of patients who received full-dose DICEP for relapsed/refractory HL or DLBCL between June 1995 and September 2018 at the Foothills Medical Centre (FMC) in Calgary, Alberta, Canada was conducted. Descriptive statistics were used to assess response rate, as defined by the 2007 International Working Group response criteria. Of the 218 patients included in this study, 87.6% of patients in the control group and 88.5% of patients in the aprepitant group responded to DICEP (difference 0.025 [95% CI, -0.066 to 0.114], p = 0.827). Univariate analyses for age, sex, type of cancer, stage of cancer, number of prior relapses, and relapse status were not significant. No significant differences were observed for secondary outcomes. Response rates to DICEP in relapsed/refractory HL and DLBCL patients were similar regardless of aprepitant use. Considering these results and the effectiveness of aprepitant in CINV, its addition to standard antiemetic therapy in patients receiving DICEP should be given strong consideration in the transplant setting.

Ocrelizumab in MS patients with persistence of disease activity after alemtuzumab: A multi-center Italian study

Background: The reason why some multiple sclerosis (MS) patients show disease activity after alemtuzumab (ALM) is still unclear, but ocrelizumab (OCR) could represent an interesting sequential therapeutic approach. Objectives: To investigate safety and efficacy of OCR in MS patients with disease activity after two ALM courses. Methods: Observational retrospective multi-centers Italian cohort study. Results: Seventy-two subjects were included. Mean follow-up (FU) was 2.4 (±1) years. Forty-five patients (62.5%) experienced at least one adverse event (AE), with infections accounting for 96.7% of cases. A reduction in total lymphocytes was observed between OCR start and 6 months FU, driven by BCD19+ lymphocytes depletion (p < 0.001). Immunoglobulin M (IgM) levels decreased between OCR start and 6 months FU (p < 0.001). At 2-year FU, relapse, magnetic resonance imaging (MRI) activity and disability worsening-free survival were 92.1%, 90.8%, and 89.2%. The evidence of inflammatory activity between the two ALM courses was associated with higher risk of relapse, MRI activity, and NEDA-3 status loss in relapsing-remitting multiple sclerosis (RRMS; p = 0.02, p = 0.05, p = 0.01, respectively). Conclusions: OCR after two ALM courses seemed to be safe and effective. Early IgM hypogammaglobulinemia occurred in a high proportion of patients. The evidence of inflammatory activity between ALM courses seemed to increase the risk of MS re-activation on OCR treatment.

The Effect of Oral Care Protocols on Mucositis in Pediatric Cancer Patients: A Randomized Controlled Trial

Background/Aims: Standard oral care protocols can reduce the incidence of mucositis. This study aimed to evaluate the effect of the "Oral Care Protocol" containing sodium bicarbonate or saline on mucositis development, degree, and duration in pediatric cancer patients. Methods: This study is a blind, parallel trial design, randomized controlled study. Patients (n = 43) who received inpatient chemotherapy treatment for more than three days at the Pediatric Hematology and Oncology Unit were included. The oral care protocol with saline was given to the patients in the control group (n = 22), and the oral care protocol with sodium bicarbonate was given to the patients in the study group (n = 21). The primary outcome was the development of mucositis. The secondary outcomes were mucositis degree, patient data at the time of mucositis development, and the duration of mucositis. The characteristics of the patients in the study and control groups and the data of patients with and without mucositis were compared with Fisher's exact test, t-test, and chi-square analysis. Results: No statistically significant difference was found between the study and control groups in terms of mean age, gender, diagnosis, relapse status, treatment stage, risk group, and treatment protocols. Mucositis developed in 18.2% of the patients in the control group and 9.5% of the patients in the study group. No statistically significant difference was found in terms of mucositis development, degree, and duration. Conclusions: The oral care protocol with sodium bicarbonate can be used to prevent mucositis in pediatric cancer patients. ClinicalTrials.gov Identifier: NCTXXX.

Outcomes of children treated for relapsed or refractory acute lymphoblastic leukemia: A single tertiary care center experience.

Acute lymphoblastic leukemia (ALL) is one of the most common malignancies among children. Despite success in frontline treatment, 20% of children will relapse or show resistance to treatment. The aim of this study is to evaluate the clinical characteristics of children diagnosed and treated for refractory or relapsed ALL and determine 3-year overall survival (OS) outcomes. This study involved a retrospective chart review of patients aged 1-14 years diagnosed with ALL during January 2002 to December 2018. Data were extracted for baseline characteristics at diagnosis and at relapse. A total of 347 newly diagnosed children with ALL were identified, among whom there were three induction failures (IF) and 28 relapses, resulting in a cohort of 31 patients with a relapse rate of 9%. The male-to-female ratio was 4.16:1, and the mean duration of first complete remission (CR1) was 26 months. Fifteen (48%) patients relapsed ≤18 months, 7 (23%) during 18-36 months, and 9 (29%) relapsed >36 months of IF or CR1. Nineteen patients (61%) had isolated bone marrow (BM) relapse, 7 (23%) patients experienced isolated extramedullary relapse (5 isolated CNS relapse and 2 isolated testicular relapse), and 5 (16%) patients experienced BM involvement with other sites (4 BM + CNS and 1 BM + testis). The 3-year OS of the cohort was 62.3%, while in patients with CR post first-salvage therapy, a 3-year OS of 79.5% was observed (p value <.05 compared with patients who did not achieve remission post first-salvage therapy, 3-year OS: 46.4%). The same statistical difference was observed in 3-year OS when comparing the duration of remission of CR prior to relapse: ≤18 months, 33.2%; 18-36 months, 66.7%; and >36 months, 87.5%. The same trend continued when comparing 3-year OS based on risk stratification at relapse: low risk (LR), 83.3%; intermediate risk (IR), 80%; and high risk (HR), 44.8%. The incidence and outcomes reported are comparable to internationally reported data regarding the duration of CR1. Risk stratification at relapse and remission status post-salvage therapy were identified as significant prognostic factors for survival. No survival difference was observed among patients who received hematopoietic stem cell transplantation after induction compared with those who received chemotherapy, which could be attributed to the smaller sample size, warranting a multi-institutional observational study. These findings corroborate the need for novel therapies and treatment approaches.

MDB-106. MEDULLOBLASTOMA TUMOR MICROENVIRONMENTS SHOW INTRA- AND INTER-TUMORAL HETEROGENEITY ON SPATIAL TRANSCRIPTOMICS

Abstract BACKGROUND Medulloblastoma defines a heterogeneous set of neuroepithelial neoplasms of the posterior fossa. Four groups of medulloblastoma are recognized: wingless (WNT), sonic hedgehog (SHH), group 3, and group 4. The tumor microenvironment (TME) influences tumor progression and response to therapy and has emerged as a growing target for the study of novel therapeutic approaches. METHODS We show spatial gene expression architecture through 10X Visium Spatial Sequencing on 16 formalin-fixed paraffin-embedded (FFPE) samples representing all molecular groups of medulloblastoma. Spatial transcriptomics data is correlated with clinical parameters, including M-stage at diagnosis, tumor histological classification, and outcomes data including survival and relapse status. RESULTS Spatial sequencing demonstrates both intra- and inter-tumoral TME heterogeneity across molecular subgroups. Unsupervised clustering and uniform manifold approximate projection illustrate clusters of distinct spatial gene expression representing cell states from different components of the TME, including tumor-associated astrocytes (TAA), macrophages (TAM), and vascular endothelium. Medulloblastoma cells constitute the majority of cells and express marker genes representing different stages of neuronal differentiation and cell cycle. Pathway analysis reveals the enrichment of pathways associated with cell motility (RHO GTPase, MET, MAPK signaling), heat shock response, growth factor signaling, and adaptive immune response (TLR, MHC-II signaling). In addition, molecular pathways known in medulloblastoma, including NF-kB and TP53 regulatory pathways, were also enriched. Neighborhood-enrichment analysis reveals the co-localization of TAMs and TAAs in close spatial relationship with mitotic progenitor-like medulloblastoma cells. Additionally, these two cell types constitute a greater proportion of the TME in patients at relapse compared to initial diagnosis. CONCLUSION Spatial transcriptomics enables new insight into the heterogeneity of the medulloblastoma TME. Notably, our analysis elucidates the spatial association of TAMs and TAAs with proliferating tumor cells and an increased abundance of these cell types following relapse. These initial results support the role of TAMs and TAAs in medulloblastoma progression.

HGG-45. HIGH GRADE GLIOMA PRESENTING AS A SYNCHRONOUS CANCER IN A PATIENT WITH DIFFUSE LARGE B CELL LYMPHOMA: A UNIQUE TREATMENT DILEMMA

Abstract BACKGROUND Patients with synchronous tumors pose significant treatment dilemmas. We present a pediatric patient found to have concomitant Diffuse Large B-cell Lymphoma (DLBCL) and a High Grade Glioma (HGG). His unique presentation and family history uncovered a familial diagnosis of Lynch Syndrome. CASE A 7-year-old male presented with acute appendiceal rupture. Surgical resection identified an appendiceal mass consistent with localized DLBCL. While undergoing staging evaluations, the patient complained of new onset blurry vision with normal neurologic and ophthalmologic exams. Subsequent imaging was concerning for a high-grade lesion. Biopsy confirmed HGG and he underwent gross total resection. Family history included a brother with relapsed leukemia status post bone marrow transplant and multiple first cousins with lymphoma and gastrointestinal cancers. RESULTS While awaiting genetics and mutational analysis, we initiated treatment. The HGG was treated with focal radiation to the tumor bed starting 2 weeks after resection. Lymphoma therapy was initiated concurrently per the REBOOT regimen with the goal of decreasing doxorubicin dosing during radiation. Lumbar punctures and intrathecal chemotherapy were deferred until completion of radiation. Biopsy of residual abdominal masses following consolidation 1 showed &amp;lt;5% viable cells and therapy was intensified to ANHL1331, Group C1. Evaluation of both lesions identified hypermutation (mutational burden &amp;gt; 150mutations/Mb). Two unique germline mutations of PMS2 were also identified, consistent with Lynch syndrome. After completion of above therapy, the patient received maintenance therapy with nivolumab checkpoint inhibition. The patient developed severe neutropenia leading to cessation of nivolumab and quick progression of his HGG. CONCLUSION Synchronous tumors pose significant treatment dilemmas given the need to treat multiple lesions while balancing side effects. While checkpoint inhibitors may provide a way to address multiple lesions, our patient had unacceptable side effects limiting the utility of this therapy.

Are people in the US getting cancer at a younger age?

e23321 Background: Advanced age is a well-known risk factor for the development of cancer. One-third of all cancer diagnoses occur in patients aged 75 or older1. In general, cancer incidence rates are very low in younger populations, with only 25 cases per 100,000 in those aged 20 years or younger and about 350 cases per 100,000 in those between the ages of 45 and 492. However, in recent years, studies have started to show an uncharacteristic rise in cancer diagnoses amongst young people in the United States. Methods: The Ipsos Oncology monitor is an online, multi-center medical chart review of oncology patients receiving drug therapy. Over 2,200 cancer treating physicians in the United States were screened for seniority and caseload and submitted data on 385,912 cancer patients (aggregate; all tumour types) between January 2018 to December 2023. Data captured included tumor type, patient age, whether the patient was newly diagnosed, follow-up or relapsed patient status and the treatment they received. Results: Reported patient age across all cancer types remained stable over time, recording an average age of 64.19 years in 2023. However, shifts in prevalence amongst younger age groups were recorded in select tumor indications. Within reported newly diagnosed breast cancer patients, the proportion of those aged 55 years or younger shifted significantly from 23% in December 2018, to 27% in December 2023. Over this same period, a similar trend was recorded in reported newly diagnosed colorectal cancer patients, with the proportion of those 55 years or younger rising from 17% to 22%. In contrast, sampled newly diagnosed melanoma and prostate patients reported decreased diagnoses in the 55 or younger age group. Conclusions: This demonstrates that the oncology patient cohort in this study remains mostly stable in age overall. However, the declining age of diagnosis in both reported breast and colorectal cancer may merit concern. These results outline the importance of robust screening efforts and suggest performance of routine screening at an earlier age may be beneficial. In addition, expansion of clinical trials and other oncology research to younger patient populations may be needed. Further investigation using comparator cohort is warranted. Age and cancer (2023) Cancer Research UK. Available at: https://www.cancerresearchuk.org/about-cancer/causes-of-cancer/age-and-cancer (Accessed: 31 January 2024). Risk factors: Age (no date) National Cancer Institute. Available at: https://www.cancer.gov/about-cancer/causes-prevention/risk/age (Accessed: 31 January 2024). Ugai, T. et al. (2022) ‘Is early-onset cancer an emerging global epidemic? current evidence and future implications’, Nature Reviews Clinical Oncology, 19(10), pp. 656–673. doi:10.1038/s41571-022-00672-8.

Medication Risks and Their Association with Patient-Reported Outcomes in Inpatients with Cancer.

We aimed to assess medication risks and determine factors influencing the health-related quality of life (HRQOL) in cancer inpatients. A retrospective analysis was conducted to identify drug-related problems (DRPs) based on medication reviews, including patient-reported outcomes (PROs). Multiple linear regression analyses were performed to identify sociodemographic, disease-related, and drug therapy-related factors influencing changes from hospital admission to discharge in the scales of the EORTC QLQ-C30 questionnaire. A total of 162 inpatients with various hematological and solid cancer diseases was analyzed. Patients received a mean of 11.6 drugs and 92.6% of patients exhibited polymedication resulting in a mean of 4.0 DRPs per patient. Based on PRO data, 21.5% of DRPs were identified. Multiple linear regression models described the variance of the changes in global HRQOL and physical function in a weak-to-moderate way. While drug therapy-related factors had no influence, relapse status and duration of hospital stay were identified as significant covariates for global HRQOL and physical function, respectively. This analysis describes underlying DRPs in a German cancer inpatient population. PROs provided valuable information for performing medication reviews. The multiple linear regression models for global HRQOL and physical function provided explanations for changes during hospital stay.

Prognostic value of circulatory growth factors to predict responsiveness to chemotherapy and remission status of patients with acute myeloid leukemia

IntroductionTumor neovascularization, an essential requirement for malignant disease progression and metastasis, depends on the dysregulation of pro-angiogenic and anti-angiogenic activities. This study aimed to investigate the utilization of circulatory angiopoietins (Ang-1 and Ang-2), vascular endothelial growth factor (VEGF-A and VEGF-C), and basic fibroblast growth factor (bFGF) as a prognostic tool for acute myeloid leukemia (AML).Material and methodsTwenty-four AML patients who were under chemotherapeutic intervention were included. Patients’ relapse status, responsiveness to chemotherapy, and remission status were obtained from their medical profiles. For comparative purposes, fifteen healthy subjects were included. Serum levels of growth factors were measured.ResultsAs compared to control subjects, AML patients had significantly lower average levels of Ang-1 (170.8 ±12.7 versus 59.2 ±12.5 ng/ml) and VEGF-A (56.0 ±13.1 versus 98.6 ±11.9 ng/dl) that coincide with a higher average level of Ang-2 (18.5 ±4.1 ng/ml versus 7.5 ±0.8 ng/ml). Spearman’s correlation analysis defined a significant association of sAng-1 and sAng-2 with patients’ response to chemotherapy ( = 0.488) and remission status ( = 0.476), respectively. According to the receiver operating characteristic (ROC) curve, downregulation of Ang-1 has good predictivity for poor responsiveness to chemotherapy (AUC = 0.781, p &lt; 0.05) while upregulation of sAng-2 has good predictivity for failed remission status (AUC = 0.779, p &lt; 0.05).ConclusionsIn the context of AML, dysregulated circulatory levels of Ang-1 and Ang-2 are suggested prognostic markers to provide useful predictivity of patients’ adverse responsiveness to chemotherapy and remission status, respectively.

Prognostic implication of methylation-based circulating tumor DNA detection prior to surgery in stage I non-small cell lung cancer

BackgroundCirculating tumor DNA (ctDNA) positivity at diagnosis, which is associated with worse outcomes in multiple solid tumors including stage I–III non-small cell lung cancer (NSCLC), may have utility to guide (neo)adjuvant therapy. MethodsIn this retrospective study, 260 patients with clinical stage I NSCLC (180 adenocarcinoma, 80 squamous cell carcinoma) were allocated (2:1) to high- and low-risk groups based on relapse versus disease-free status ≤5 years post-surgery. We evaluated the association of preoperative ctDNA detection by a plasma-only targeted methylation-based multi-cancer early detection (MCED) test with NSCLC relapse ≤5 years post-surgery in the overall population, followed by histology-specific subgroup analyses. ResultsAcross clinical stage I patients, preoperative ctDNA detection did not associate with relapse within 5 years post-surgery. Sub-analyses confined to lung adenocarcinoma suggested a histology-specific association between ctDNA detection and outcome. In this group, ctDNA positivity tended to associate with relapse within 2 years, suggesting prognostic implications of MCED test positivity may be histology- and time-dependent in stage I NSCLC. Preoperative ctDNA detection was associated with upstaging of clinical stage I to pathological stage II–III NSCLC. ConclusionsOur findings suggest preoperative ctDNA detection in patients with resectable clinical stage I NSCLC using MCED, a pan-cancer screening test developed for use in an asymptomatic population, has no detectable prognostic value for relapse ≤5 years post-surgery. MCED detection may be associated with early adenocarcinoma relapse and increased pathological upstaging rates in stage I NSCLC. However, given the exploratory nature of these findings, independent validation is required.

Inflammatory and neurodegenerative serum protein biomarkers increase sensitivity to detect clinical and radiographic disease activity in multiple sclerosis

The multifaceted nature of multiple sclerosis requires quantitative biomarkers that can provide insights related to diverse physiological pathways. To this end, proteomic analysis of deeply-phenotyped serum samples, biological pathway modeling, and network analysis were performed to elucidate inflammatory and neurodegenerative processes, identifying sensitive biomarkers of multiple sclerosis disease activity. Here, we evaluated the concentrations of > 1400 serum proteins in 630 samples from three multiple sclerosis cohorts for association with clinical and radiographic new disease activity. Twenty proteins were associated with increased clinical and radiographic multiple sclerosis disease activity for inclusion in a custom assay panel. Serum neurofilament light chain showed the strongest univariate correlation with gadolinium lesion activity, clinical relapse status, and annualized relapse rate. Multivariate modeling outperformed univariate for all endpoints. A comprehensive biomarker panel including the twenty proteins identified in this study could serve to characterize disease activity for a patient with multiple sclerosis.

A PET-based radiomics nomogram for individualized predictions of seizure outcomes after temporal lobe epilepsy surgery

PurposeTo establish and validate a novel nomogram based on clinical characteristics and [18F]FDG PET radiomics for the prediction of postsurgical seizure freedom in patients with temporal lobe epilepsy (TLE). Patients and Methods234 patients with drug-refractory TLE patients were included with a median follow-up time of 24 months after surgery. The correlation coefficient redundancy analysis and LASSO Cox regression were used to characterize risk factors. The Cox model was conducted to develop a Clinic-PET nomogram to predict the relapse status in the training set (n = 171). The nomogram's performance was estimated through discrimination, calibration, and clinical utility. The prognostic prediction model was validated in the test set (n = 63). ResultsEight radiomics features were selected to assess the radiomics score (radscore) of the operation side (Lat_radscore) and the asymmetric index (AI) of the radiomics score (AI_radscore). AI_radscor, Lat_radscor, secondarily generalized seizures (SGS), and duration between seizure onset and surgery (Durmon) were significant predictors of seizure-free outcomes. The final model had a C-index of 0.68 (95 %CI: 0.59–0.77) for complete freedom from seizures and time-dependent AUROC was 0.65 at 12 months, 0.65 at 36 months, and 0.59 at 60 months in the test set. A web application derived from the primary predictive model was displayed for economic and efficient use. ConclusionsA PET-based radiomics nomogram is clinically promising for predicting seizure outcomes after temporal lobe epilepsy surgery.

Abstract 3668: Plasma cell-free DNA profiling for deciphering cellular origins and immune competence in cancer patients

Abstract Plasma cell-free DNA (cfDNA) originates from apoptotic cells in the blood, providing a real-time insight into the biology of various cell types. The fragment coverage pattern of cfDNA across the genome is known to reflect the distinct chromatin status of originating cells. While extensive research has focused on fragments derived from cancer, known as circulating tumor DNA (ctDNA), for inference about cancer biology, cfDNA fragments from healthy cells have received little attention. Our study explores the potential of cfDNA to decipher the relative abundance of distinct blood cell types, particularly immune system cell types. We collected a cohort of 273 bladder (BC) and colorectal cancer (CRC) patients and 45 healthy controls for plasma whole genome sequencing and assessed the fragment coverage profile at transcription start sites (TSS) of protein coding genes. A significant negative correlation was observed between TSS coverage and whole blood gene expression (Spearman’s rho = -0.65). Furthermore, TSS coverage revealed a bimodal distribution, characterized by modes corresponding to high and low gene expression levels in blood cells. This may suggest the cfDNA coverage profile as a binary expression status classifier to distinguish between expressed and unexpressed genes in blood cells. We further evaluated TSS with differential coverage between age groups of healthy individuals and relapse status of cancer patients. Notably, out of the TSS that significantly differentiated middle-aged (aged 40-65) from older individuals (aged 65+), 31 were also able to distinguish relapse from non-relapse patients. Among these TSS were CD36, SLAMF7, TABBP and PDCD1, known to be involved in immune related pathways. Finally, we evaluated coverage at cell-type specific TSS and found dendritic cells (P-value: CRC = 8e-06, BC = 5.1e-3), monocytes (CRC = 1.6e-04, BC = 2.5e-3), and NK cells (CRC = 8.5e-04, BC = 0.026) to exhibit a significant increase in coverage in the cancer cohorts compared to healthy controls. Conversely, T-cells showed a decrease in coverage (CRC = 0.041, BC = 0.062). In conclusion, cfDNA coverage profile may identify TSS with differential coverage between patient groups and characterize a shift in blood cell type composition as a response to cancer. Future work may show if fragment coverage quantifies the relative contribution of cfDNA from distinct immune cell types. We anticipate our analysis to illuminate the utility of plasma cfDNA as a biomarker for cancer patient’s immune competency, enabling improved patient stratification for treatment, leveraging their distinct immune capabilities. Citation Format: Laura Andersen, Amanda Frydendahl, Tenna Vesterman Henriksen, Christina Demuth, Mads Heilskov Rasmussen, Iver Nordentoft, Karin Birkenkamp-Demtröder, Jakob Skou Pedersen, Søren Besenbacher, Lars Dyrskjøt, Claus L. Andersen, Nicolai J. Birkbak. Plasma cell-free DNA profiling for deciphering cellular origins and immune competence in cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3668.

Treatment modifiers across different regimens of natalizumab treatment in MS: An Italian real-world experience

Despite its widespread use in clinical practice, the effectiveness of natalizumab extended interval dosing (EID) adopted from treatment start across different treatment intervals and individual modifiers (body mass index - BMI) is still under-investigated. Here, seven-hundred and forty-five multiple sclerosis (MS) patients, exposed to natalizumab for 3.30 ​± ​1.34 years, were retrospectively enrolled in an observational multicenter study. After stratifying patients in EID or standard interval dosing (SID), we assessed differences in time to relapse, MRI activity and Expanded Disability Status Scale (EDSS) progression. The primary analysis was conducted on patients exposed to EID interval from 5 weeks and 1 day to 7 weeks, while a secondary analysis included also EID periods up to 8 weeks. An additional analysis explored the impact of BMI. No differences in time to first relapse, time to radiological activity, time to EDSS progression or time to EDA (evidence of disease activity) were detected between SID and EID group (EID interval from 5 weeks to 1 day to 7 weeks). When including EID periods from 7 weeks and 1 day to 8 weeks, the EID group showed a trend towards higher risk of experience clinical relapses than the SID group. A higher EDA risk was also identified in EID patients with BMI above median. In conclusion, a higher risk of relapses seems to occur for EID above 7 weeks. Independently from the EID scheme adopted, higher BMI increases the risk of EDA in these patients.