Predictors Of Relapse Research Articles

Prognostic significance of lymphovascular space invasion in early-stage low-grade endometrioid endometrial cancer: a fifteen-year retrospective Chinese cohort study

ObjectiveIn 2016, the ESMO-ESGO-ESTRO consensus included LVSI (Lymph-vascular space invasion, LVSI) status as a risk stratification factor for stage I endometrioid endometrial cancer (EEC) patients and as one of the indications for adjuvant therapy. Furthermore, LVSI is included in the new FIGO staging of endometrial cancer (EC) in 2023. However, the data contribution of the Chinese population in this regard is limited. The present study aimed to further comfirm the influence of LVSI on the prognosis of early-stage low-grade EEC in a fifteen-year retrospective Chinese cohort study.MethodsThis retrospective analysis cohort included 702 EEC patients who underwent TAH/BSO surgery, total abdominal hysterectomy, bilateral salpingooophorectomy in Peking University People’s Hospital from 2006 to 2020. Patients were stratified based on LVSI expression status as: LVSI negative group and LVSI positive group. Clinical outcome measures related to LVSI, assessed with a univariate and multivariate Cox proportional hazards regression model.Results702 EEC patients with stage I and grade 1–2 were analyzed. 58 patients (8.3%) were LVSI-positive and 14 patients (2.0%) was relapse. Recurrence rates in LVSI-negative and LVSI-positive were 1.6% and 6.9%, respectively. 5-year disease-free survival (DFS) rate in LVSI-negative and LVSI-positive were 98.4% and 93.1%, respectively. These rates for 5-year overall (OS) survival in LVSI-negative were 98.9% while it was 94.8% in LVSI-positive. Multivariate analysis showed that LVSI is an independent risk factor for 5-year DFS (HR = 4.60, p = 0.010). LVSI has a similar result for 5-year OS(HR = 4.39, p = 0.028).ConclusionsLVSI is an independent predictor of relapse and poor prognosis in early-stage low-grade endometrioid endometrial cancer in the Chinese cohort.

Narrative review on ethical and psychological issues raised by genetic and genomic testing in pediatric oncology care.

In pediatric oncology, genetic and genomic tests are proposed throughout the care pathway for many reasons (e.g., cancer characterization, identification of the most appropriate treatment, patient selection for clinical trials, identification of tissue/organ donors, or risk of relapse prediction). Despite the many different approaches (somatic or germline testing, targeted gene or genome sequencing), the implicated individuals are confronted with situations that may intersect and that are interesting to compare. No study has identified and analyzed the available works on these new practices in pediatric oncology. The aim of this narrative literature review was to describe the ethical and psychological perspectives of children with cancer, parents, and healthcare professionals when genetic or genomic testing is proposed as part of the cancer management. Eighteen articles met the inclusion criteria and were comprehensively coded using MAXQDA. Their analysis showed that concerning the subjective implications of genetic and genomic testing, the areas of ambivalence (desire of treatment, desire for knowledge, uncertainty, and guilt) reported by patients and their parents seem to mirror the healthcare professionals' concerns. The ethical and psychological issues about predisposition testing, long discussed in the context of hereditary retinoblastoma and Li-Fraumeni syndrome, represent a useful starting point for a wider discussion of a genetic and genomic testing pathway in pediatric oncology more broadly.

Smartphone-based markers of social connectivity in schizophrenia and bipolar disorder

Social isolation and social impairment are hallmarks of progression as well as predictors of relapse in psychiatric disorders. We conducted a pilot study to assess the feasibility of sensing the social activity phenotype and loneliness using active and passive markers collected using a smartphone application. The study included 9 schizophrenia and bipolar disorder patients followed in the Bipolar Longitudinal study for at least 1 month and for whom mobile communication data was collected using the Beiwe smartphone application. Subjects completed daily surveys on digital and in-person social activity, and feelings of being outgoing or lonely. We described the level and variability of social activity features. We employed k-means clustering to identify “important contacts”. Further, we investigated whether social network-derived features of mobile communication are independent predictors of weekly counts of outgoing calls and text, weekly average self-reported digital social activity, and loneliness using mixed effect models and clustering with dynamic time warping distance. Subjects were followed between 5 and 208 weeks (number of days of observation = 2538). The k-means cluster analysis approach identified the number of “important contacts” among close friends and family members as reported in clinical interviews. The cluster analysis and longitudinal regression analysis indicate that the number of individuals a person communicates with on their phone is an independent predictor of perceived loneliness, with stronger evidence when “important contacts” only are included. This study provides preliminary evidence that the number of “important contacts” a person communicates with on their phone is a promising marker to capture subjects’ engagement in mobile communication activity and perceived loneliness.

Association of circulating tumor DNA with patient prognosis in surgically resected renal cell carcinoma.

Despite complete resection, 20%-50% of patients with localized renal cell carcinoma (RCC) experience recurrence within 5 years. Accurate assessment of prognosis in high-risk patients would aid in improving outcomes. Here we evaluate the use of circulating tumor DNA (ctDNA) in RCC using banked samples and clinical data from a single institution. The cohort consisted of 45 RCC patients (≥pT1b) who underwent complete resection. The presence of ctDNA in plasma was determined using a personalized, tumor-informed ctDNA assay (Signatera RUO, Natera, Inc.). Relationships with outcomes and other relevant clinical variables were assessed. The median follow-up was 62 months. Plasma ctDNA was detected in 18 out of 36 patients (50%) pre-operatively and was associated with increased tumor size (mean 9.3 cm vs. 7.0 cm, P < .05) and high Fuhrman grade (60% grades III-IV vs 27% grade II, P = .07). The presence of ctDNA, either pre-operatively or at any time post-operatively, was associated with inferior relapse-free survival (HR = 2.70, P = .046; HR = 3.23, P = .003, respectively). Among patients who were ctDNA positive at any time point, the sensitivity of relapse prediction was 84% with a PPV of 90%. Of note, ctDNA positivity at a post-surgical time point revealed a PPV of 100% and NPV of 64%. The lack of ctDNA detection at both time points yielded an NPV of 80%. Detection of plasma ctDNA using a personalized assay is prognostic of recurrence in patients with resected RCC. Herein, we describe a successful approach for its application and identify potential limitations to be addressed in future studies.

Exploring Pattern of Relapse in Pediatric Patients with Acute Lymphocytic Leukemia and Acute Myeloid Leukemia Undergoing Stem Cell Transplant Using Machine Learning Methods.

Background. Leukemic relapse remains the primary cause of treatment failure and death after allogeneic hematopoietic stem cell transplant. Changes in post-transplant donor chimerism have been identified as a predictor of relapse. A better predictive model of relapse incorporating donor chimerism has the potential to improve leukemia-free survival by allowing earlier initiation of post-transplant treatment on individual patients. We explored the use of machine learning, a suite of analytical methods focusing on pattern recognition, to improve post-transplant relapse prediction. Methods. Using a cohort of 63 pediatric patients with acute lymphocytic leukemia (ALL) and 46 patients with acute myeloid leukemia (AML) who underwent stem cell transplant at a single institution, we built predictive models of leukemic relapse with both pre-transplant and post-transplant patient variables (specifically lineage-specific chimerism) using the random forest classifier. Local Interpretable Model-Agnostic Explanations, an interpretable machine learning tool was used to confirm our random forest classification result. Results. Our analysis showed that a random forest model using these hyperparameter values achieved 85% accuracy, 85% sensitivity, 89% specificity for ALL, while for AML 81% accuracy, 75% sensitivity, and 100% specificity at predicting relapses within 24 months post-HSCT in cross validation. The Local Interpretable Model-Agnostic Explanations tool was able to confirm many variables that the random forest classifier identified as important for the relapse prediction. Conclusions. Machine learning methods can reveal the interaction of different risk factors of post-transplant leukemic relapse and robust predictions can be obtained even with a modest clinical dataset. The random forest classifier distinguished different important predictive factors between ALL and AML in our relapse models, consistent with previous knowledge, lending increased confidence to adopting machine learning prediction to clinical management.

Single–dose high-dose-rate brachytherapy versus two and three fractions for locally advanced prostate cancer

BackgroundSingle-dose high-dose-rate brachytherapy (SD-HDR-BT) was compared to two or three fraction HDR BT in intermediate and high-risk localized prostate cancer with median follow-up of 10 years. Materials and methods293 patients received 1 × 19Gy or 1 × 20Gy (Group A = 49), 2 × 13Gy (Group B = 138), or 3 × 10.5 Gy (Group C = 106) HDR BT. The primary endpoint was biochemical relapse-free interval (bRFI). Late genitourinary (GU) and gastrointestinal (GI) morbidity used RTOG scales and the International Prostate Symptom Score (IPSS). Freedom from biochemical relapse (bRFI), overall survival (OS) and GU, GI and IPSS morbidity were calculated using Kaplan-Meier (K-M) method and log-rank test. Univariate and multivariate hazard ratios (HR) were obtained using Cox’s proportional hazard. ResultsAt 10 years, K-M estimates of bRFI were 64 % (Group A), 72 % (Group B), and 76 % (Group C) (p = 0.2). No statistically significant difference was seen in OS. In multivariate analysis risk-category and ADT administration, but not dose, were significant predictors of relapse (p = 0.0003 and 0.03, respectively). At ten years, GU grade 3 events were 8 % (A), 2 % (B) and 13 % (C); (p = 0.01). IPSS ≥ 20 was 31 % (A), 20 % (B) and 23 % (C); (p = 0.6) and grade 3 GI was 0 % in groups A and B and 2 % in C; (p = 0.3). No GU or GI grade-4 events were observed. Pre-treatment IPSS was a highly significant predictor of failure in multivariate analysis. ConclusionsLong-term outcome data show reduced but not statistically significant difference in PSA control, and no difference in overall survival, between SD-HDR-BT and 2 or 3 fractions of HDR-BT.

Clinical outcome predictors for metastatic renal cell carcinoma: a retrospective multicenter real-life case series

Over the last decades, the therapeutic armamentarium of metastatic renal cell carcinoma (mRCC) has been revolutionized by the advent of tyrosin-kinase inhibitors (TKI), immune-checkpoint inhibitors (ICI), and immune-combinations. RCC is heterogeneous, and even the most used validated prognostic systems, fail to describe its evolution in real-life scenarios. Our aim is to identify potential easily-accessible clinical factors and design a disease course prediction system. Medical records of 453 patients with mRCC receiving sequential systemic therapy in two high-volume oncological centres were reviewed. The Kaplan-Meier method and Cox proportional hazard model were used to estimate and compare survival between groups. As first-line treatment 366 patients received TKI monotherapy and 64 patients received ICI, alone or in combination. The mean number of therapy lines was 2.5. A high Systemic Inflammation Index, a BMI under 25 Kg/m2, the presence of bone metastases before systemic therapy start, age over 65 years at the first diagnosis, non-clear-cell histology and sarcomatoid component were correlated with a worse OS. No significant OS difference was observed between patients receiving combination therapies and those receiving exclusively monotherapies in the treatment sequence. Our relapse prediction system based on pathological stage and histological grade was effective in predicting the time between nephrectomy and systemic treatment. Our multicentric retrospective analysis reveals additional potential prognostic factors for mRCC, not included in current validated prognostic systems, suggests a model for disease course prediction and describes the outcomes of the most common therapeutic strategies currently available.

Measurable residual disease testing by next generation sequencing is more accurate compared with multiparameter flow cytometry in adults with B-cell acute lymphoblastic leukemia

Results of measurable residual disease (MRD)-testing by next-generation sequencing (NGS) correlate with relapse risk in adults with B-cell acute lymphoblastic leukemia (ALL) receiving chemotherapy or an allotransplant from a human leukocyte antigen (HLA)-identical relative or HLA-matched unrelated donor. We studied cumulative incidence of relapse (CIR) and survival prediction accuracy using a NGS-based MRD-assay targeting immunoglobulin genes after 2 courses of consolidation chemotherapy cycles in 93 adults with B-cell ALL most receiving HLA-haplotype-matched related transplants. Prediction accuracy was compared with MRD-testing using multi-parameter flow cytometry (MPFC). NGS-based MRD-testing detected residual leukemia in 28 of 65 subjects with a negative MPFC-based MRD-test. In Cox regression multi-variable analyses subjects with a positive NGS-based MRD-test had a higher 3-year CIR (Hazard Ratio [HR] = 3.37; 95 % Confidence Interval [CI], 1.34–8.5; P = 0.01) and worse survival (HR = 4.87 [1.53–15.53]; P = 0.007). Some data suggest a lower CIR and better survival in NGS-MRD-test-positive transplant recipients but allocation to transplant was not random. Our data indicate MRD-testing by NGS is more accurate compared with testing by MPFC in adults with B-cell ALL in predicting CIR and survival. (Registered in the Beijing Municipal Health Bureau Registration N 2007-1007 and in the Chinese Clinical Trial Registry [ChiCTR–OCH–10000940 and ChiCTROPC-14005546]).

O-282 Detection and elimination of malignant cells from cryopreserved testis and ovarian tissue?

Abstract For young patients receiving treatments that might impair their reproductive functions, gonadal tissue cryopreservation emerges as a technique to preserve their future fertility. The reimplantation of cryopreserved prepubertal gonadal tissue is currently the most promising strategy for restoring fertility in these individuals. There have been reports of successful births after autotransplanting ovarian tissue harvested at peri-puberty. In males, although autotransplantation of testicular tissue has not yet led to the production of viable sperm, successful reproduction has been documented in primate studies following such procedures. The preservation of gonadal tissue in the setting of cancer introduces concerns regarding the potential for malignant cell contamination, leading to worries about the future reimplantation of contaminated tissue. Recent analysis shows significant contamination rates with cancer cells in cryopreserved gonadal tissues from children with leukemia and lymphoma — 37% in testicular tissues and 12% in ovarian tissues. The risk of contamination extends beyond hematological cancers with documented cases of cancer cell contamination in ovarian tissue from patients with apparently localized sarcoma, and detection of neuroblastoma cells in cryopreserved testicular tissue. Such significant contamination rates prompt discussions about harvesting tissue post-chemotherapy, although gonadotoxic treatments may adversely affect the quality of the cryopreserved germ cells. Emerging diagnostic techniques, especially molecular methods, are being investigated for their ability to more accurately detect residual maliganat disease. While traditional histology and immunohistochemistry have been the norm, their sensitivity is relatively low. More precise molecular-genetic techniques, such as Polymerase Chain Reaction (PCR) and Reverse Transcriptase-quantitative PCR, demonstrate greater sensitivity. Moreover, advanced methods like next-generation sequencing offer even higher precision in detecting minimal residual disease. Xenotransplantation of gonadal tissue into immunodeficient animals may also provide some insights as a preclinical method for relapse prediction. Future research is essential to refine these diagnostic techniques to achieve the necessary sensitivity for clinical application. This presentation aims to explore the current knowledge on gonadal tissue contamination rates for both hematological cancers and solid tumors in prepubertal patients and to review strategies for decontaminating gonadal tissues. A critical examination of existing knowledge gaps will be conducted with the objective of identifying secure methods for fertility restoration in cancer survivors.

The Core outcome Clubfoot (CoCo) study: relapse, with poorer clinical and quality of life outcomes, affects 37% of idiopathic clubfoot patients.

There is a lack of high-quality research investigating outcomes of Ponseti-treated idiopathic clubfeet and correlation with relapse. This study assessed clinical and quality of life (QoL) outcomes using a standardized core outcome set (COS), comparing children with and without relapse. A total of 11 international centres participated in this institutional review board-approved observational study. Data including demographics, information regarding presentation, treatment, and details of subsequent relapse and management were collected between 1 June 2022 and 30 June 2023 from consecutive clinic patients who had a minimum five-year follow-up. The clubfoot COS incorporating 31 parameters was used. A regression model assessed relationships between baseline variables and outcomes (clinical/QoL). Overall, 293 patients (432 feet) with a median age of 89 months (interquartile range 72 to 113) were included. The relapse rate was 37%, with repeated relapse in 14%. Treatment considered a standard part of the Ponseti journey (recasting, repeat tenotomy, and tibialis anterior tendon transfer) was performed in 35% of cases, with soft-tissue release and osteotomies in 5% and 2% of cases, respectively. Predictors of relapse included duration of follow-up, higher initial Pirani score, and poor Evertor muscle activity. Relapse was associated with poorer outcomes. This is the first multicentre study using a standardized COS following clubfoot treatment. It distinguishes patients with and without relapse in terms of clinical outcomes and QoL, with poorer outcomes in the relapse group. This tool allows comparison of treatment methods and outcomes, facilitates information sharing, and sets family expectations. Predictors of relapse encourage us to create appropriate treatment pathways to reduce relapse and improve outcome.

Description and Prognosis of Patients with Recovered Dilated Cardiomyopathy: A Retrospective Cohort Study.

With the recent advances in the treatment of heart failure (HF), it is intriguing that a very small number of patients with dilated cardiomyopathy (DCM) have been observed as being fully recovered. However, knowledge of the progression and prognosis of patients with recovered DCM remains sparse. Herein, we conducted this study to investigate the clinical characteristics and prognosis of patients with recovered DCM. Consecutive patients with recovered DCM referred to our hospital between March 2009 and May 2021 were included. The recovered DCM patients were categorized into relapse and non-relapse groups. The primary endpoint was all-cause death, and the secondary endpoint was HF re-hospitalization during follow-up. Multivariate analyses were performed to identify predictors of relapse among recovered DCM patients. Kaplan-Meier analyses were used to assess the prognostic significance of relapse. A comparatively large cohort of 122 recovered DCM patients from 10,029 DCM patients was analyzed. During a median follow-up duration of 53.5 months, the relapse rate among recovered DCM patients was 15.6% (19/122). Age (odds ratio, OR 1.079, 95% confidence interval, CI: 1.014-1.148; p = 0.017), systolic blood pressure (SBP) at diagnosis (OR 0.948, 95% CI: 0.908-0.990; p = 0.015) and changes in left ventricular ejection fraction from diagnosis to recovery ( LVEF) (OR 0.898, 95% CI: 0.825-0.978; p = 0.013) were identified as predictors of relapse. Furthermore, among 122 patients, 5 (4.1%) experienced death, and 12 (9.8%) underwent HF re-hospitalization. Four deaths occurred in the relapse group, with one in the non-relapse group. All deaths were attributed to cardiovascular events. The long-term prognosis of the relapse group was significantly worse compared to the non-relapse group by Kaplan-Meier analysis (p 0.001 based on the log-rank test). Multivariate analyses significantly associated relapse with all-cause mortality in recovered DCM patients (hazard ratio, HR 7.738, 95% CI: 1.892-31.636; p = 0.004). Recovered DCM patients are at risk of relapse. Older age, lower SBP, and smaller LVEF were independently associated with relapse in recovered DCM patients. Relapse after recovery was related to an unfavorable long-term prognosis.

Predictors of Success and Relapse after Desmopressin Monotherapy for Monosymptomatic Nocturnal Enuresis

Predictors of Success and Relapse after Desmopressin Monotherapy for Monosymptomatic Nocturnal Enuresis

Architectural dysplasia in surgical margins and the risk of local relapse in oral cancer.

A major challenge in the clinical management of oral cavity squamous cell carcinoma is local relapse. Even when surgical margins are tumor-free, local relapses occur frequently, and relapse prediction by histology remains suboptimal. In leukoplakia, an oral potentially malignant disorder, the presence of architectural dysplasia is a critical risk factor for malignant transformation. This study aimed to investigate whether the presence of architectural dysplasia in oral cavity squamous cell carcinoma surgical margins is a risk factor for local relapse. Hematoxylin and eosin-stained slides of resection margins from a consecutive cohort of surgically treated patients diagnosed with stage I-IV oral cavity squamous cell carcinoma between 2008 and 2014 were assessed for the presence of architectural dysplasia (N = 311). Five-year local relapse-free survival rates of oral cavity squamous cell carcinoma with architectural dysplasia were compared to those of oral cavity squamous cell carcinoma without architectural dysplasia. In total, 92 of 311 (29.6%) of oral cavity squamous cell carcinoma displayed architectural dysplasia in the margins. The presence of architectural dysplasia was associated with higher patient age, female sex, less pack years, lower cT-stage, and a cohesive tumor growth pattern. In oral cavity squamous cell carcinomas with architectural dysplasia, postoperative (chemo)radiotherapy was less often indicated compared with oral cavity squamous cell carcinoma without architectural dysplasia (19.5% vs. 36.1%, p = 0.009). Five-year local relapse-free survival was significantly lower in oral cavity squamous cell carcinoma with architectural dysplasia than in oral cavity squamous cell carcinoma without architectural dysplasia (83.1% vs. 94.9%, p = 0.017). Oral cavity squamous cell carcinoma arising in the background of architectural dysplasia displays relatively favorable clinical and histopathological characteristics. Nonetheless, the presence of architectural dysplasia in oral cavity squamous cell carcinoma surgical margins is associated with a higher risk of local relapse, indicating its clinical relevance.

Identification of a circular RNA isoform of WASHC2A as a prognostic factor for high-risk paediatric B-ALL patients

Pediatric B-cell acute lymphoblastic leukemia (B-ALL) is a serious disease for which a better understanding of prognostic factors and new therapeutic targets is needed. Circular RNAs (circRNAs) are promising markers due to their stability and differential expression patterns in various diseases. However, their role in pediatric B-ALL patients, particularly in risk stratification and relapse prediction, remains poorly understood. In this study, we comprehensively examined the circRNA landscape in pediatric B-ALL patients, focusing on both high-risk and standard-risk patients. Using advanced sequencing techniques and sophisticated bioinformatics tools, we identified thousands of circRNAs, including a novel circRNA derived from the WASHC2A gene, termed circWASHC2A. CircWASHC2A showed differential expression between high-risk and standard-risk patients and exhibited potential for predicting relapse in high-risk patients. Functional experiments highlighted a role for circWASHC2A in regulating cell cycle progression and mitochondrial respiratory activity in leukaemic cells. Transcriptomic analysis further supported these findings, suggesting the involvement of circWASHC2A in signalling pathways relevant to leukaemia pathogenesis. This study provides in-depth insights into the circRNA landscape of pediatric B-ALL patients and identifies circWASHC2A as a potential biomarker for risk stratification and relapse prediction, with significant implications for tailoring diagnostic and therapeutic strategies in this patient population.

Analyzing the predictors of relapse in drug-induced headache: a prospective clinical and psychological study

Analyzing the predictors of relapse in drug-induced headache: a prospective clinical and psychological study

Depression-Anxiety Coupling Strength as a predictor of relapse in major depressive disorder: A CAN-BIND wellness monitoring study report

BackgroundA critical challenge in the study and management of major depressive disorder (MDD) is predicting relapse. We examined the temporal correlation/coupling between depression and anxiety (called Depression-Anxiety Coupling Strength, DACS) as a predictor of relapse in patients with MDD. MethodsWe followed 97 patients with remitted MDD for an average of 394 days. Patients completed weekly self-ratings of depression and anxiety symptoms using the Quick Inventory of Depressive Symptoms (QIDS-SR) and the Generalized Anxiety Disorder 7-item scale (GAD-7). Using these longitudinal ratings we computed DACS as random slopes in a linear mixed effects model reflecting individual-specific degree of correlation between depression and anxiety across time points. We then tested DACS as an independent variable in a Cox proportional hazards model to predict relapse. ResultsA total of 28 patients (29 %) relapsed during the follow-up period. DACS significantly predicted confirmed relapse (hazard ratio [HR] 1.5, 95 % CI [1.01, 2.22], p = 0.043; Concordance 0.79 [SE 0.04]). This effect was independent of baseline depressive or anxiety symptoms or their average levels over the follow-up period, and was identifiable more than one month before relapse onset. LimitationsSmall sample size, in a single study. Narrow phenotype and comorbidity profiles. ConclusionsDACS may offer opportunities for developing novel strategies for personalized monitoring, early detection, and intervention. Future studies should replicate our findings in larger, diverse patient populations, develop individual patient prediction models, and explore the underlying mechanisms that govern the relationship of DACS and relapse.

Optimizing perioperative treatment for potentially resectable stage III squamous cell lung carcinoma: promising results of a condensed four-cycle regimen with tislelizumaband chemotherapy

BackgroundThe standard care for resectable non-small cell lung cancer (NSCLC) involves perioperative therapy combining chemotherapy and immune checkpoint inhibitors, typically lasting 6 to 12 months. However, the optimal treatment strategies for potentially resectable squamous cell lung carcinoma (SCC) remain unclear. This Phase 2 trial aimed to assess the efficacy and safety of a condensed four-cycle perioperative treatment regimen with tislelizumab combined with chemotherapy in patients with potentially resectable stage III SCC.MethodsPatients with potentially resectable stage IIIA-IIIB (N2) SCC received intravenous tislelizumab, albumin-bound paclitaxel, and carboplatin for up to four cycles. The primary endpoints were major pathologic response (MPR) and incidence of treatment-related adverse events. Safety and potential biomarkers for efficacy prediction were also assessed.ResultsAmong 35 enrolled patients, 32 underwent surgery with R0 resection achieved in all cases. MPR was achieved in 24 patients and pathological complete response (pCR) in 14 patients. Radiographic objective response was observed in 31 patients. The 12-month and 24-month event-free survival rate was 85.7 and 61.0%, respectively. Four patients experienced grade 3 or 4 adverse events. Tumor tissue based next-generation sequencing revealed the potential associations between several biomarkers and pathological response, including tumor neoantigen burden score, 18-gene expression profile score, CD8 + T cells, M1/M2 macrophages ratio and interferon‐gamma expression level. Besides, circulating tumor DNA (ctDNA) dynamics and concentration were also associated with pathological response and the presence of ctDNA at postoperative month 1 was a strong predictor for disease relapse. Furthermore, metagenomic sequencing in bronchoalveolar lavage fluid demonstrated Streptococcus was the most abundant genus in the pCR group.ConclusionsA condensed four-cycle perioperative treatment regimen of tislelizumab combined with chemotherapy demonstrated promising efficacy and manageable toxicities in potentially resectable stage III SCC. Specific biomarkers showed potential for predicting treatment efficacy and the mechanism of superior antitumor response of pCR patients was preliminarily and indirectly explored.Trial registrationClinicalTrials.gov, NCT05024266. Registered August 27, 2021.

Clinical application of individualized tumor-informed circulating tumor DNA for therapeutic response and relapse prediction in patients with neuroblastoma.

10053 Background: Patients with high-risk neuroblastoma (NB) generally present with widely metastatic disease and often relapse despite intensive therapy. At present, circulating tumor DNA (ctDNA)-based minimal residual disease (MRD) has been studied in various tumors and proven to be valuable in guiding treatment and predicting recurrence, but its application in NB has rarely been reported. This study aimed to assess the effectiveness of tumor-informed ctDNA monitoring for evaluating the response to induction therapy in NB patients, as well as its role in predicting the risk of relapse. Methods: We conducted a prospective cohort study of NB patients. Primary tumor samples were collected at baseline and blood samples were collected sequentially from baseline until disease progression or the last follow-up. Tumor tissue samples were subjected to whole exome sequencing (WES), and clonal mutations were selected for the individualized MRD panel. Sequencing was conducted at OrigiMed, a College of American Pathologists accredited and Clinical Laboratory Improvement Amendments certified laboratory. Results: Our cohort included 43 individuals diagnosed with NB, with a median age of 3.5 years (0.42-40 years). WES revealed that 75% (2054/2753) of the mutated genes were unique to each patient, and 98.9% (704/712) of the selected tumor-informed single nucleotide variants were variants of unknown significance, suggesting that individualized tumor-informed MRD (n = 23) is superior to fixed tumor-agnostic panel (n = 20) MRD in NB. A successful individualized MRD panel was constructed for 53.5% (23/43) of patients, with a remarkable 92.3% success rate for those older than 5 years (p &lt; 0.01). The initial positivity rate for ctDNA detection was 68%, with the initial positivity rate being associated with the stage (p &lt; 0.01). During treatment and follow-up, 0/6 of the patients whose ctDNA levels remained negative experienced a relapse, whereas 2/5 patients who had a negative conversion or an increase in positivity experienced a relapse. In addition, ctDNA changes matched radiological evaluations in 94% of patients. Notably, ctDNA was detected prior to radiological relapse, with a lead time of 6 months in one patient. Patients can be divided into four groups according to the mutation landscape: ALK mutation, MYCN amplification, chromosome amplification, and other groups. Among them, the rate of ctDNA clearance was the highest in the chromosome amplification group, indicating that patients in this group were the most sensitive to chemotherapy. Conclusions: Individualized tumor-informed ctDNA monitoring shows promise for evaluating therapeutic response and forecasting relapse in NB patients. This approach proves more effective than fixed tumor-agnostic panel-based MRD due to high genetic mutation uniqueness. Clinical trial information: NCT05076071 .

Blood-based inflammatory protein biomarker panel for the prediction of relapse and severity in patients with neuromyelitis optica spectrum disorder: A prospective cohort study.

To date, most existing models for predicting neuromyelitis optica spectrum disorder (NMOSD) are based primarily on clinical characteristics. Blood-based NMOSD severity and prognostic predictive immune- and inflammation-related biomarkers are needed. We aimed to investigate the associations between plasma inflammatory biomarkers and relapse and attack severity in NMOSD. This two-step, single-center prospective cohort study included discovery and validation cohorts. We quantified 92 plasma inflammatory proteins by using Olink's proximity extension assay and identified differentially expressed proteins in the relapse group (relapse within 1 year of follow-up) and severe attack group. To define a new molecular prognostic model, we calculated the risk score of each patient based on the key protein signatures and validated the results in the validation cohort. The relapse prediction model, including FGF-23, DNER, GDNF, and SLAMF1, predicted the 1-year relapse risk. The severe attack prediction model, including PD-L1 and MCP-2, predicted the severe clinical attack risk. Both the relapse and severe attack prediction models demonstrated good discriminative ability and high accuracy in the validation cohort. Our discovered biomarker signature and prediction models may complement current clinical risk stratification approaches. These inflammatory biomarkers could contribute to the discovery of therapeutic interventions and prevent NMOSD progression.

Short-term and long-term survival outcomes in patients with invasive lobular carcinoma vs. invasive ductal carcinoma of the breast.

e12564 Background: Invasive lobular carcinoma (ILC) accounts for 10% of all invasive breast cancer and has distinct histological and biological features compared to the most common breast cancer histological subtype, invasive ductal carcinoma (IDC). ILC is more endocrine sensitive and chemotherapy resistant than IDC and has a different metastatic pattern. There is lack of conclusive data on the differences in survival outcomes between ILC and IDC. We aimed to assess the short-term and long-term survival outcomes in patients with ILC and IDC in a large population database. Methods: This is a retrospective, population-based study using data from the Surveillance, Epidemiology, and End Results database. We included women &gt; 18 years with stage I-III ILC or IDC diagnosed from 1992-2020. Multivariable logistic regression was used to assess factors associated with different treatment modalities in patients with IDC vs. ILC. We estimated breast cancer-specific survival (BCSS) using Kaplan-Meier methods and their survival rates were compared using the log-rank test. We analyzed BCSS at different time points using a cox regression model with time-varying coefficients. Results: 343,397 patients with IDC and 39,859 patients with ILC were included in this study. Patients with ILC were older (63.0 ± 12.5 years vs. 59.2 ± 13.5 years, p&lt;0.001). There were more non-Hispanic white patients with ILC vs. IDC (76% vs. 67%, p&lt;0.001). Patients with ILC had more advanced disease: more stage III disease (16% vs. 11%, p&lt;0.001), more T3-T4 disease (15% vs. 6%, p&lt;0.001), and more N2-N3 disease (12% vs. 9%, p&lt;0.001). Patients with ILC also had a higher frequency of hormone receptor positive disease (97% vs. 81%, p&lt;0.001). Fewer patients with ILC had grade 3-4 tumors (9% vs. 36%, p&lt;0.001). Our multivariate analysis showed that compared to patients with IDC, patients with ILC were more likely to undergo mastectomy (OR=1.85, p &lt; 0.001) and radiation (OR=1.20, p&lt;0.001), but less likely to receive chemotherapy (OR= 0.92, p&lt;0.001). After adjusting for clinicopathological features, treatment modalities, and socioeconomic variables; compared to patients with IDC, patients with ILC had better BCSS in the first five years (HR=0.71, p &lt;0.001), but worse BCSS in later years (HR=1.30, p&lt;0.001 in year 6-10; HR=1.75, p&lt;0.001 in year 11-15; HR=2.17, p&lt;0.001 in year 16-20). Annual hazard models show that IDC peaked at recurrence in the first 5 years after diagnoses, and the hazard rate declines gradually after that. ILC peaked at recurrence in the first 5 years after diagnosis with minimal decrease in hazard rates after that. Conclusions: BCSS of patients with ILC is better in early years but worse in later years compared to patients with IDC. Future studies are needed to identify predictors of late relapses in ILC, and novel therapeutic strategies are required for these patients.