Risk Of Progression In Patients Research Articles

Trastuzumab Duocarmazine in Pretreated Human Epidermal Growth Factor Receptor 2-Positive Advanced or Metastatic Breast Cancer: An Open-Label, Randomized, Phase III Trial (TULIP).

Human epidermal growth factor receptor 2 (HER2)-targeted therapy is standard of care for HER2-positive (HER2+) breast cancer, but most patients develop progressive disease with persistent HER2 expression. No definitive treatment guidance currently exists beyond second line. Trastuzumab duocarmazine (T-Duo) is a third-generation, HER2-targeted antibody-drug conjugate that demonstrated efficacy and acceptable safety in phase I studies of heavily pretreated patients with HER2+/HER2-low breast cancer. In this open-label, randomized, phase III trial, T-Duo was compared with physician's choice (PC) in patients with unresectable locally advanced/metastatic HER2+ breast cancer with progression during/after ≥2 HER2-targeted therapies or after trastuzumab emtansine (T-DM1). The primary endpoint was progression-free survival (PFS) by blinded independent central review. In total, 437 patients were randomly assigned 2:1 to T-Duo (n = 291) or PC (n = 146). The median age was 56.0 years (range, 24-86); most patients (93.6%) had metastatic disease. The median time from diagnosis of metastatic disease to trial entry was 3.5 years; the median number of prior HER2-targeted therapies in metastatic setting was three. The median PFS was 7.0 months (95% CI, 5.4 to 7.2) with T-Duo versus 4.9 months (95% CI, 4.0 to 5.5; hazard ratio [HR], 0.64 [95% CI, 0.49 to 0.84]; P = .002) with PC. PFS benefit was maintained across most predefined subgroups. The median overall survival (first analysis) was 20.4 (T-Duo) versus 16.3 months (PC; HR, 0.83 [95% CI, 0.62 to 1.09]; P = .153). Objective response rate was 27.8% (T-Duo) versus 29.5% (PC); other efficacy end points-clinical benefit rate, duration of response, and reduction in target lesion measurement-tended to favor T-Duo. Grade ≥3 treatment-emergent adverse events occurred in 52.8% (T-Duo) versus 48.2% (PC). Treatment with T-Duo was manageable, but tolerability was affected by prevalent ocular toxicity, leading to a higher discontinuation rate in the T-Duo arm. T-Duo significantly reduced the risk of progression in patients with advanced HER2+ breast cancer who have progressed during/after ≥2 HER2-targeted therapies or after T-DM1.

Proteomic Profiling Identifies Predictive Signatures for Progression Risk in Patients with Advanced-Stage Follicular Lymphoma.

Background: Follicular lymphoma (FL) is characterized by an indolent nature and generally favorable prognosis, yet poses a particular clinical challenge, since disease progression is observed in a notable subset of patients. Currently, it is not possible to anticipate which patients will be at risk of progression, highlighting the need for reliable predictive biomarkers that can be detected early in the disease. Methods: We applied tandem-mass-tag labelled nano-liquid chromatography tandem mass spectrometry (nLC-MS/MS) on 48 diagnostic formalin-fixed, paraffin-embedded tumor samples from patients with advanced-stage FL. Of these, 17 experienced subsequent progression (subsequently-progressing, sp-FL) while 31 did not (non-progressing, np-FL). Results: We identified 99 proteins that were significantly differentially expressed between sp-FL samples and np-FL samples (p < 0.05; log2-fold changes between 0.2 and -1.3). Based on this subset of proteins, we classified patients into high-risk and low-risk subgroups using unsupervised machine learning techniques. Pathway analyses of the identified proteins revealed aberrancies within the immune system and cellular energy metabolism. In addition, two proteins were selected for immunohistochemical evaluation, namely stimulator of interferon genes 1 (STING1) and isocitrate dehydrogenase 2 (IDH2). Notably, IDH2 retained significantly lower expression levels in sp-FL samples compared with np-FL samples (p = 0.034). Low IDH2 expression correlated with shorter progression-free survival (PFS, p = 0.020). Conclusions: This study provides evidence for some of the biological mechanisms likely to be involved in FL progression and, importantly, identifies potential predictive biomarkers for improvement of risk stratification up-front at time of FL diagnosis.

Neutrophil-to-lymphocyte ratio as a predictor of progression in patients with early-stage cervical cancer

Aims: The neutrophil-to-lymphocyte ratio (NLR) has shown promise as a prognostic marker in various cancers, but its role in early-stage cervical cancer is not well defined. This study evaluates the association between pre-treatment NLR and progression risk in patients with early-stage cervical cancer. Methods: This retrospective study included 220 patients with stage I and II cervical cancer treated from 2010 to 2024. Patients with prior treatment, infection at diagnosis, or hematological diseases were excluded. Pre-treatment NLR was calculated from blood counts taken within a week before treatment. Primary outcome was progression-free survival (PFS). Cox regression analyses identified prognostic factors. Results: The median follow-up was 46 months (range, 1-120). Disease progression occurred in 17.3% of patients, and 15% died. The 5-year overall survival and PFS rates were 84.8% (95% CI: 79.3-90.3) and 77.7% (95% CI: 71.4-84), respectively. Univariate analysis identified non-squamous cell carcinoma (non-SCC) histology, tumor size &gt;4 cm, and elevated NLR as significant factors affecting PFS. Multivariate analysis confirmed non-SCC histology (HR: 3.2, p=0.002), tumor size &gt;4 cm (HR: 2.3, p=0.007), and elevated NLR (HR: 1.1, p=0.041) as independent PFS risk factors. Higher NLR correlated with larger tumor size. Conclusions: Elevated pre-treatment NLR independently predicts disease progression in early-stage cervical cancer. Incorporating NLR into risk stratification could enhance prognostic assessments and guide personalized treatments. Larger prospective studies are needed for validation.

Lactate drives epithelial-mesenchymal transition in diabetic kidney disease via the H3K14la/KLF5 pathway

High levels of urinary lactate are an increased risk of progression in patients with diabetic kidney disease (DKD). However, it is still unveiled how lactate drive DKD. Epithelial-mesenchymal transition (EMT), which is characterized by the loss of epithelial cells polarity and cell-cell adhesion, and the acquisition of mesenchymal-like phenotypes, is widely recognized a critical contributor to DKD. Here, we found a switch from oxidative phosphorylation (OXPHOS) toward glycolysis in AGEs-induced renal tubular epithelial cells, thus leading to elevated levels of renal lactic acid. We demonstrated that reducing the lactate levels markedly delayed EMT progression and improved renal tubular fibrosis in DKD. Mechanically, we observed lactate increased the levels of histone H3 lysine 14 lactylation (H3K14la) in DKD. ChIP-seq & RNA-seq results showed histone lactylation contributed to EMT process by facilitating KLF5 expression. Moreover, KLF5 recognized the promotor of cdh1 and inhibited its transcription, which accelerated EMT of DKD. Additionally, nephro-specific knockdown and pharmacological inhibition of KLF5 diminished EMT development and attenuated DKD fibrosis. Thus, our study provides better understanding of epigenetic regulation of DKD pathogenesis, and new therapeutic strategy for DKD by disruption of the lactate-drived H3K14la/KLF5 pathway.

Durability of immune checkpoint inhibitor (ICI) response following treatment discontinuation in advanced merkel cell carcinoma (MCC).

9596 Background: Advanced MCC has a high response rate to ICI therapy, but the durability of responses once treatment is discontinued remains unclear. We therefore reviewed the long-term outcomes of advanced MCC patients at our institution who discontinued ICI treatment after achieving favorable initial response. Methods: In an IRB-approved single institution retrospective review of advanced MCC patients, we analyzed all patients who received at least one dose of anti-PD(L)1 monotherapy for unresectable or metastatic disease, achieved stable disease (SD) or better, and discontinued treatment for a reason other than disease progression. Duration of response and outcomes of subsequent therapy were assessed. Results: Of 195 advanced MCC patients treated with ICI, we identified 45 who met study criteria. Of these, 21 (47%) had a complete response (CR) to initial ICI treatment, 23 (51%) a partial response (PR) and 1 (2%) SD. Twenty-five (56%) patients discontinued ICI electively and 20 (44%) discontinued due to toxicity. In total, 21 of the 45 patients (47%) experienced disease progression at a median of 11.2 months (range 2.1-22.7 months) from ICI cessation. The median follow-up after ICI discontinuation for patients who have not experienced progression is 22.8 months (5.8-82.0 months). There was a lower rate of progression in patients who achieved CR vs. non-CR (24% vs 67%, p=0.006) and a trend towards a lower rate in those who discontinued electively vs. due to toxicity (36% vs 60%, p=0.14). For patients in whom the molecular subtype was known, there was a higher risk for progression in patients with viral MCC (12 of 16, 75%) compared to UV-associated MCC (4 of 13, 31%, p=0.02). Fifteen of the 21 patients (71%) who experienced progression were rechallenged with ICI therapy, including both single agent (12 patients, 57%) and combination (3, 14%) therapy. The remaining patients received locally-directed therapy only (3, 14%), chemotherapy (1, 5%), declined further treatment (1, 5%), or transferred care and were lost to follow up (1, 5%). Eleven of 15 ICI-retreated patients (73%) achieved an objective response to rechallenge, including all 3 patients who received combination therapy with ipilimumab+nivolumab. Twelve of the 45 patients have expired; 6 due to progressive MCC and remaining 6 known or suspected from unrelated causes. Conclusions: Patients with advanced MCC have a substantial risk of disease progression following treatment discontinuation despite initial favorable ICI response, 47% in our series with a median time to event of 11.2 months, particularly in those that achieve less than a complete response. In the setting of disease progression post-ICI discontinuation, most patients maintain sensitivity to retreatment with the same drug class. Virus-positive MCC may be a risk factor for post-discontinuation relapse, which should be validated in future studies.

The prognostic value of circulating miRNAs in patients with localized/locally advanced prostate cancer after radical prostatectomy and radiotherapy.

184 Background: The outcome after curative intended management of local prostate cancer (PC) is promising. However, there is still a risk of biochemical relapse (BR) after either radical prostatectomy (RP) or radiotherapy (RT). MicroRNAs (miRNAs) have showed encouraging results as alternative biomarkers in different settings of PCa. The aim of this study was to investigate the prognostic value of circulating miRNAs after management of local PCa. Methods: In total 107 newly diagnosed patients with local or locally advanced PCa were included in the study. The cohort was divided into an interventional group with 59 patients (RP (39 patients) or RT (20 patients)) and an observational group with 48 patients (active surveillance (AS)). Both baseline samples at time of diagnosis and follow-up samples six months after treatment were collected. The relative expression of four miRNAs (miRNA-21, -93, -125b, and miRNA-221) was assessed in plasma using real-time polymerase chain reaction. Results: In the interventional cohort, the decrease in miRNA-125b after RT was significantly associated with a longer time to biochemical recurrence (BR) (HR= 0.17, p=0.03), and a higher level of miRNA-125b at baseline samples showed a tendency to higher risk for BR in the same population (HR= 2.82, p=0.09). On the other hand, lower levels of miRNA-221 at both baseline and follow-up samples tended to be associated with lower risk of BR in patients managed by RT (HR=0.14, p=0.07, and HR=0.13, p=0.07, respectively). None of these four miRNAs was associated with a significant risk of progression in patients managed by AS. Conclusions: Both baseline and the dynamics of miRNA-125b was informative as to the risk of BR in patients with PCa treated by RP. Validation in independent cohorts is called for.

Advances in the Treatment of Keratoconus: Epithelial-On (EPI-On) Corneal-Collagen Cross-Linking (CXL) and CXL-Plus Procedures.

Keratoconus (KC) incidence is on the increase. The advent of corneal-collagen cross-linking (CXL) has revolutionized the management of KC. This systematic review looks at the efficacy and complications of two novel treatments within CXL: Epithelial-On (Epi-On) and CXL-plus procedures. Two separate literature searches were carried out up until July 1, 2021. Articles only published in the last two years were included to ensure that only the most recent articles were reviewed. A total of 15 articles were selected for this review. There were varied results regarding the efficacy of Epi-On.No significant difference was found between Epi-On and standardEpithelial-Off (Epi-Off) CXL. However, it was found that Epi-On was inferior to standard CXL in terms of reducing KMAX. There was a higher risk of progression in patients treated with Epi-On CXL, with an increased rate of patients requiring re-treatment due to the advancement of their KC. While some studies report CXL-plus procedures demonstrate long-term efficacy and safety, a considerable number of studies advise caution, reporting a significant deterioration in corrected distance visual acuity (CDVA). Consequently, a question persists regarding the safest and most efficacious approach, given the lack of robust large randomized controlled trials (RCTs) in the current literature.

Cell Free MYC DNA Copy Number Identifies High-Risk Smouldering Myeloma and Newly Diagnosed Multiple Myeloma

Introduction Smouldering multiple myeloma (SMM) is a heterogenous condition, with some patients progressing rapidly (high-risk) while others have MGUS-like disease (low-risk). The International Myeloma Working Group's (IMWG) 2/20/20 risk score predicts 2-year progression, but despite these improvements in risk-stratification, identification of patients requiring early intervention remains elusive. For newly diagnosed multiple myeloma (NDMM), survival varies, and current risk-stratification falls short for poor responders to standard first-line therapy (high-risk). MYC is a potent oncogene implicated in the initiation, maintenance, and progression of various malignancies. MYC overexpression on immunohistochemistry predicts poor clinical outcome in MM 1, implicating MYC overexpression in aggressive disease kinetics in MM. We hypothesised that MYC copy number could improve identification of high-risk SMM and ND MM. In this study, we developed a minimally invasive liquid biopsy approach to characterise the expression of MYC copy number in circulating cell-free DNA (cfDNA) on a unique cohort of peripheral blood samples obtained from the national liquid biopsy biobank, the M1000 that is linked to our clinical registry, the Myeloma and Related Diseases Registry (MRDR). Methods We obtained plasma samples from 64 SMM and 149 ND MM patients from the M1000. cfDNA was extracted from 1mL of plasma collected in Streck™ tubes using QIAamp Circulating Nucleic Acid Kit (QIAGEN) according to manufacturer instructions. Equal amount of cfDNA (5 uL), run in duplicates, from each patient was utilised for copy number assessment developed using the Biorad QX200 Digital Droplet TM PCR. The copy number of MYC was calculated by comparing the number of molecules (using a ratio of positive to negative droplets) to the number of molecules arising from the reference (RPP30) genomic locus using the QuantaSoft TM Analysis Pro Software (Biorad). MYC copy number were correlated with clinical data from MRDR on progression in SMM and overall survival (OS) in NDMM. We use median copy number as cut off to categorise high and low MYC. Results We were able to extract cfDNA from 1 ml of plasma samples from both SMM and NDMM patients, with the median amount being 35.11 ng (11.9 ng - 107.78ng) and 50.26 ng (5.85 ng - 243.45 ng), respectively. The median MYC copy number levels were 1.883 in SMM and 1.860 for NDMM. Within 36 months follow up in the SMM cohort, 18 patients progressed to MM with median time to progression of 14 months (2- 36 months, Figure 1). High MYC copy number (&amp;gt;1.9) at diagnosis was predictive of disease progression with hazard ratio of 5.27 (95% CI 1.99 -14; P = 0.0015). When combined with the 20/20/20 risk stratification model 3, MYC copy number improved the reliability of this score. In the NDMM cohort, median OS for the cohort was not reached at 36 months follow up. Patients with high MYC copy number (&amp;gt;1.9) at diagnosis had shorter OS at 36 months compared to those with low MYC copy number at 36 months (66.05% vs 82.02%. P=0.0012, Figure 2). Conclusion Our study demonstrates a significant association between MYC copy number, assessed via plasma cfDNA, and the risk of progression in patients with SMM. Additionally, in NDMM, MYC copy number at diagnosis directly correlates with OS. These findings require further investigation and validation in a larger cohort of M1000 samples, as they have the potential to introduce a minimally-invasive risk stratification methodology to identify high-risk patients and the introduction of MYC targeted therapies in patients with high MYC copy number.

Monoclonal Protein Concentration and Risk of Multiple Myeloma: Is 0.5 g/DL the New 1.5?

Introduction : Monoclonal Gammopathy of Undetermined Significance (MGUS) is an asymptomatic clonal plasma cell disorder with a risk of progression to multiple myeloma (MM). To provide an accurate prognosis, monoclonal protein (M-protein) concentration has been used to assess risk of progression to myeloma. Current risk models developed from stored serum samples in a predominately white population of patients indicated a low risk of progression (less than 1% per year) in patients with M-protein of &amp;lt;1.5 g/dL. Little is known about M-protein concentration and risk of progression in patients tested during routine clinical care in a more diverse population. We assessed the outcomes of MGUS five years after diagnosis, and determined the association between baseline characteristics and the rate of progression to MM. Methods: We used data from national Veterans Health Administration system to identify patients diagnosed with MGUS from 1999-2021 and were followed from MGUS diagnosis until progression, death, or the date 7/11/2023 was reached. MGUS diagnosis and progression to MM was confirmed utilizing a natural language processing algorithm. We included patients of black and white race and those with IgG, IgA, or light chain MGUS. The exposure was M-protein concentration at MGUS diagnosis, stratified by ≤0.5, &amp;gt;0.5-≤1.0, &amp;gt;1.0-≤1.5, &amp;gt;1.5 g/dL. We plotted the cumulative incidence function curve and used a multivariable Fine-Gray sub distribution hazard model with progression at 5 years as the event of interest, and death as a competing event. Covariates included sex, race, MGUS type, age, body mass index (BMI), diabetes, renal disease, and other comorbidities summarized by Charlson Comorbidity Index at MGUS diagnosis. Results: We included 15,520 patients with MGUS. The mean age at the diagnosis was 71.1. IgG subtype was more common (83.2%) than IgA (12.7%), and light chain (4.1%). 19.6% and 39.5% of patients had renal disease and diabetes, respectively. Black veterans represented 5600 (36.1%) of the cohort. At 5 years, 26.6% of veterans with an M-protein of &amp;gt;1.5 g/dL were diagnosed with myeloma, compared to 11.7% with 1.1-1.5 g/dL, 6.9% with 0.6-1.0 g/dL, and 3.3% with ≤0.5 g/dL. In multivariable models an M-protein &amp;gt;1.5 was associated with a greater risk of progression compared to ≤0.5 (multivariable-adjusted Hazard Ratio [aHR] 9.76, 95% Confidence Interval [CI] 8.37-11.40). Overall, increasing age was shown to have lower risk of transitioning to MM at 5 years with aHR of 0.983 (95% CI 0.978-0.988). Conclusion: In this modern cohort, only an M-protein of ≤0.5 g/dL was associated with a less 1% per year risk of developing MM. Conversely, 26.6% of veterans with an M-protein level &amp;gt;1.5 g/dL developed MM at 5 years. Risk of MM in patients clinically evaluated for MGUS may be higher than previously thought and new models of MM progression should be developed.

Development of a LC–MS/MS analytical method of 15 compounds related to renal function for a prognostic method of progression risk in patients with diabetic kidney disease

Diabetic kidney disease (DKD) onset and progression is a major cause of end-stage renal failure in diabetic patients, however, no practical method has been reported to predict the progression rate of renal function decline. Nine serum compounds are reported to associate with prognosis in type 1 diabetes patients; however, quantitative analytical methods for these compounds lacks. Herein, we developed a simultaneous quantitative method for 15 compounds, including Niewczas’s nine biomarker candidates, associated with renal function and its prognosis in kidney disease patients to achieve a prognostic method of renal function decline in DKD patients. This report describes the development and validation of a LC–MS/MS analytical method for 15 compounds of biomarker candidates using human plasma, serum, and urine as sample matrices. The analytes are N-acetyl-L-alanine, N6-acetyl-L-lysine, N-acetyl-L-serine, N-acetyl-L-threonine, phenyl sulfate, pseudouridine, N6-threonylcarbamoyladenosine, tryptophan 2-C-mannoside, tyrosine O-sulfate, creatinine, p-cresol sulfate, 4-ethylphenyl sulfate, indoxyl sulfate, N1-methyladenosine, and trimethylamine N-oxide. The Capcell Pak ADME-HR column was compared to several general columns and selected as the most suitable column for the simultaneous analysis of all 15 compounds. The proposed method was validated for selectivity, accuracy, precision, stability, dilution integrity, and parallelism. This report describes the suitability of the calibration ranges established and the actual sample concentrations of serum and urine from type 2 diabetic patients, as well as new findings on the unknown analyte levels of several compounds in these samples. The proposed method can be used to aid the development of prognostic methods for renal function decline in patients with DKD.

P134 - Risk for progression in patients with pathological lymph-node metastatic disease (pN1) who underwent robot-assisted radical prostatectomy and extensive pelvic lymph node dissection.

P134 - Risk for progression in patients with pathological lymph-node metastatic disease (pN1) who underwent robot-assisted radical prostatectomy and extensive pelvic lymph node dissection.

Exploring the Prognostic and Predictive Roles of Ki-67 in Endometrial Cancer

Background: Up to now, endometrial cancer (EC) treatments are mainly represented by surgery followed by adjuvant chemotherapy or radiotherapy. The updated guidelines give a 2A recommendation for the use of hormone therapy only in advanced low-grade ECs, underlying the need for more data on the role of hormone therapy in the adjuvant setting. Methods: The clinicopathological data of 158 early-stage EC patients was retrospectively collected. A Ki-67 cut-off value of 40% was established based on literature data. Disease-free survival (DFS) and Overall survival (OS) were evaluated. Results: Results: Multivariate analysis of DFS and OS showed a significantly increased risk of progression in patients with &gt;40% Ki-67 [HR = 3.13 (95% CI; 1.35–7.14); p = 0.007] and a significantly higher relative risk of death [HR = 3.70 (95% CI; 1.69–8.33); p = 0.001]. The predictive role of the Ki-67 index was highlighted by the clinical benefit of adjuvant hormone in patients with high Ki-67. Conclusions: Our results suggest a positive role of the Ki-67 index as a prognostic and potentially predictive marker in EC, although further studies are warranted to reach a definitive conclusion.

Risk factors for fibrosis progression in non-alcoholic steatohepatitis: Analysis of the European cohort in the real-world GAIN study

ObjectiveTo better understand drivers of disease progression in non-alcoholic steatohepatitis (NASH), we assessed clinical and sociodemographic markers of fibrosis progression in adults with NASH. Patients and methodsPhysician-reported patient demographics and clinical characteristics were utilised from the real-world Global Assessment of the Impact of NASH (GAIN) study. Factors associated with likelihood of fibrosis progression since NASH diagnosis were identified using a logistic regression model. ResultsOverall, 2349 patients in Europe from the GAIN study were included; mean age was 54.6 years and 41% were women. Significant covariates included age, years since diagnosis, employment status, fibrosis stage at diagnosis, type 2 diabetes mellitus, hypertension, liver transplant and liver biopsy at diagnosis. Risk of progression was 1.16 (95% confidence interval 1.12–1.20; p<0.001) times higher for each additional year since NASH diagnosis and 5.43 (2.68–11.37; p<0.001) times higher when physicians proposed a liver transplant at diagnosis. Compared with full-time employed patients, risk of progression was 1.77 (1.19–2.60; p=0.004) times higher for unemployed patients and 3.16 (1.30–7.63; p=0.010) times higher for those unable to work due to NASH. ConclusionsDisease duration, NASH severity and presence of other metabolic comorbidities could help to assess risk of progression in patients with NASH.

Kasa İnvaze Olmayan Mesane Kanserinde Sistemik İmmün-İnflamasyon İndeksi ve Nötrofil-Lenfosit Oranının Hastalık Nüksü ve İlerleme Riski ile İlişkisi

Objective: Some systemic inflammatory response-based biomarkers are promising for predicting prognosis of non-muscle-invasive bladder cancer (NMIBC) patients and can contribute to the risk classification without any significant cost. We aimed to evaluate the neutrophil-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) for the prediction of recurrence and progression risk in patients with NMIBC. Material and Methods: The study included a retrospective analysis of 211 patients who underwent transurethral resection of bladder (TURB) in a tertiary referral center between 2015 and 2019. The receiver operating characteristic (ROC) curve was used to determine the cut-off value. The Kaplan-Meier curves and the log-rank test were constructed to evaluate the recurrence-free and progression-free survival rates according to different levels of inflammatory markers. The multivariate regression analysis was undertaken to estimate the independent prognostic factors. Results: The optimal cut-off value of SII was found to be 568 in the ROC analysis. According to the multivariate analysis, the SII value, number of tumors at the time of initial TURB, and European Organization for Research and Treatment of Cancer (EORTC) recurrence classification were statistically significant parameters in predicting recurrence. While tumor size, NLR, and SII achieved statistically significant levels in the univariate analysis, they didn’t have significance in the multivariate analysis. Conclusion: The SII, number of tumors, and EORTC recurrence classification are prognostic parameters that can be used in the assessment of recurrence. However, inflammatory parameters do not have the same predictive ability in the prediction of the progression rate.

P-090 Clinical characteristics and risk of progression in patients with monoclonal gammopathy of uncertain significance: long-term experience in a single tertiary hospital

P-090 Clinical characteristics and risk of progression in patients with monoclonal gammopathy of uncertain significance: long-term experience in a single tertiary hospital

POSTER: MM-341 Clinical Characteristics and Risk of Progression in Patients With Monoclonal Gammopathy of Uncertain Significance (MGUS): Long-Term Experience in a Single Tertiary Hospital

POSTER: MM-341 Clinical Characteristics and Risk of Progression in Patients With Monoclonal Gammopathy of Uncertain Significance (MGUS): Long-Term Experience in a Single Tertiary Hospital

MM-341 Clinical Characteristics and Risk of Progression in Patients With Monoclonal Gammopathy of Uncertain Significance (MGUS): Long-Term Experience in a Single Tertiary Hospital

MM-341 Clinical Characteristics and Risk of Progression in Patients With Monoclonal Gammopathy of Uncertain Significance (MGUS): Long-Term Experience in a Single Tertiary Hospital

The Association of Pregnancy with Disease Progression in Patients Previously Treated for Differentiated Thyroid Cancer: A Propensity Score-Matched Retrospective Cohort Study.

Background: Differentiated thyroid cancer (DTC) is increasingly common in women of reproductive age. However, whether pregnancy increases the risk of DTC progression/recurrence after treatment remains controversial. The study aimed to assess the association of pregnancy with risk of progression in patients previously treated for DTC. Methods: This was a retrospective cohort study following 123 pregnant women and 1376 nonpregnant women at Peking University Third Hospital after initial treatment for DTC between January 2012 and December 2022. To control the effect of confounding, we carefully matched pregnancy (n = 107) and nonpregnancy groups (n = 298) in terms of baseline characteristics by using propensity score matching (PSM). Results: At baseline, the pregnancy and nonpregnancy groups were balanced in all matched variables. At follow-up, the percentage of DTC progression in the two groups was 12 (11.8%) and 47 (15.8%), respectively. Regression models showed no evidence of association of pregnancy with the risk of progression (odds ratio: 0.74 and 95% confidence interval: 0.37-1.50; p = 0.404), and remained consistent across long/short follow-up and other subgroup variables. We found that the shorter the time interval between treatment and pregnancy, the higher the risk of DTC progression (ptrend = 0.019). Conclusions: The risk of DTC progression in pregnant women was not higher than that in the well-matched, nonpregnant women. For young women previously treated for DTC, disease progression might not be a concern for their future pregnancy plan, but it seems safer to wait at least 1 year before pregnancy compared with immediate pregnancy.

Real-world Outcomes and Predictive Biomarkers for 177Lutetium Prostate-specific Membrane Antigen Ligand Treatment in Metastatic Castration-resistant Prostate Cancer: A European Association of Urology Young Academic Urologists Prostate Cancer Working Group Multi-institutional Observational Study

BackgroundThe European Association of Urology guidelines include the lutetium-177 (177Lu) PSMA-617 prostate-specific membrane antigen (PSMA) ligand as a therapy option for metastatic castration-resistant prostate cancer (mCRPC). A major challenge in clinical practice is to pursue a personalized treatment approach based on robust predictive biomarkers. ObjectiveTo assess the performance of 177Lu PSMA in real-world practice and to elaborate clinical biomarkers for evaluating treatment responses. Design, setting, and participantsWe conducted a retrospective observational study including 233 patients with mCRPC treated with 177Lu PSMA in eight high-volume European centers. Outcome measurements and statistical analysisBaseline characteristics and clinical parameters during and after 177Lu PSMA treatment were documented. Correlations to treatment response were analyzed using χ2 and log-rank tests, with differences between groups with and without disease progression calculated using a Mann-Whitney U test. Univariate and multivariate-adjusted hazard ratios (HRs) were measured using Cox proportional hazards models. Results and limitationsA prostate-specific antigen (PSA) decrease of ≥30% was observed in 41.7%, 63.5%, and 77.8% of patients after the first, second, and third treatment cycle, respectively. Restaging performed via PSMA positron emission tomography-computed tomography revealed that 33.7% of patients had an imaging-based response, including two patients with a complete response, while 13.4% had stable disease. The median time to progression was 5 mo and the median time until the start of a consecutive antineoplastic therapy was 8.5 mo. Of importance, a PSA decrease ≥30% after the first two cycles of 177Lu PSMA (1 cycle: p = 0.0003; 2 cycles: p = 0.004), absolute PSA after the first three cycles (1 cycle: p = 0.011; 2 cycles: p = 0.0005; 3 cycles: p = 0.002), and a PSA doubling time >6 mo (p = 0.009) were significantly correlated to treatment response. Furthermore, gamma-glutamyl transferase ≤31 U/L at the start of 177Lu PSMA therapy was correlated with 1.5 times higher risk of progression for patients without but not with visceral metastases (p = 0.046). Conclusions177Lu PSMA is an effective treatment option in mCRPC in the real-world setting. A PSA decrease ≥30% after the first two cycles is an early marker of response that can be easily implemented in clinical practice. Patient summary177Lu PSMA is a radioactive agent approved for treatment of advanced prostate cancer. We reviewed its use outside of clinical trials for patients treated at eight European centers. We found that 177Lu PSMA is an effective treatment option in real-world practice. A PSA (prostate-specific antigen) decrease of ≥30% after the first two therapy cycles is an early indicator of response to treatment and can be used in personalizing treatments for patients.

Progressive fibrotic interstitial lung disease.

Many interstitial lung diseases (ILDs) share mechanisms that result in a progressive fibrosing phenotype. In Brazil, the most common progressive fibrosing interstitial lung diseases (PF-ILDs) are chronic hypersensitivity pneumonitis, idiopathic pulmonary fibrosis, unclassified ILD, and connective tissue diseases. PF-ILD is seen in approximately 30% of patients with ILD. Because PF-ILD is characterized by disease progression after initiation of appropriate treatment, a diagnosis of the disease resulting in fibrosis is critical. Different criteria have been proposed to define progressive disease, including worsening respiratory symptoms, lung function decline, and radiological evidence of disease progression. Although the time elapsed between diagnosis and progression varies, progression can occur at any time after diagnosis. Several factors indicate an increased risk of progression and death. In the last few years, antifibrotic drugs used in patients with idiopathic pulmonary fibrosis have been tested in patients with PF-ILD. The effects of nintedanib and placebo have been compared in patients with PF-ILD, a mean difference of 107.0 mL/year being observed, favoring nintedanib. The U.S. Food and Drug Administration and the Brazilian Health Regulatory Agency have approved the use of nintedanib in such patients on the basis of this finding. Pirfenidone has been evaluated in patients with unclassified ILD and in patients with other ILDs, the results being similar to those for nintedanib. More studies are needed in order to identify markers of increased risk of progression in patients with ILD and determine the likelihood of response to treatment with standard or new drugs.