Median Progression Time Research Articles

DOP088 Speed of disease progression as hallmark of Crohn’s Disease Severity: The rapid and slow progressors.

Abstract Background The natural course of Crohn's Disease (CD) can involve the development of intra-abdominal strictures and fistulae (Montreal B2 and B3 phenotypes, respectively). Yet, the speed of disease progression to these phenotypes may differ among patients. This study retrospectively analyses a large cohort of CD patients with luminal phenotype at diagnosis (Montreal B1) and evaluates the speed of disease progression to B2/B3 phenotypes, in a tertiary centre in Belgium. Methods A total of 1,262 IBD patients were screened from the 3000+ inflammatory bowel diseases (IBD) patient’s clinics. Among the 516 CD patients diagnosed after 1999 and meeting the inclusion criteria, 372 presented with a B1 phenotype at diagnosis. Of these, 108 patients progressed to B2/B3 phenotypes during follow-up (FU) and were analysed. Demographics, dynamic disease characteristics and treatment adaptations were collected. Patients were stratified into rapid progressors (within 5 years) and slow progressors (beyond 5 years), based on the median progression time in our cohort of 108 patients (median 5 years [1.8-9.9], Figure 1a). Statistical analyses were performed using Prism. Results Of the 108 patients progressing to B2/B3 phenotypes, 56 (52%) were rapid progressors (median time 1.8 years [0.8–3.5]) and 52 (48%) were slow progressors (median time 10 years [7.0–12.6]; p<0.0001) (Figure 1b). Rapid progressors were older at CD diagnosis (median age 25 years [21–38] vs 19 years [15–24], p<0.0001), as paediatric CD was more prevalent in slow progressors (33% vs 5%, p=0.0003). Although both groups required biologics and surgeries in similar proportions, rapid progressors started biologics earlier (median 1.3 years [0.3–3.1] vs 5.6 years [2.7–8.9], p<0.0001) and underwent surgery for disease progression earlier (median 2 years [1.1–4.3] vs 10 years [6.9–13.4], p<0.0001). All surgeries occurred after B2/B3 progression and slow progressors underwent surgery later after initiating biologics (median 6.7 year [2–9.5] vs 1.2 year [0.3–2.7], p<0.0001 – Figure 1d). Conclusion CD patients with initial B1 phenotype progressing to B2/B3 phenotypes can be classified as rapid and slow progressors based on their speed of progression to these phenotypes. Rapid progressors demonstrate a more aggressive disease course, with earlier biologics initiation and need for surgery. The description of disease progression may uncover a new dynamic disease phenotype of disease severity that is often overlooked or lacking in the current reported cohort and population-based studies. Stratification by the speed of progression may better define patients with severe disease, potentially guiding tailored therapeutic strategies.

Clinical impact of a subtype of urothelial carcinoma in nonmuscle-invasive bladder cancer.

This study aimed to assess the oncological outcomes of the subtype of urothelial carcinoma (SUC), including divergent differentiation and histologic subtype, in comparison with those of pure urothelial carcinoma (PUC) in nonmuscle-invasive bladder cancer. We retrospectively evaluated patients who were initially treated with transurethral resection of the bladder tumor (TURBT) between March 2005 and August 2020 at a single institution. Patients with PUC and SUC were compared in terms of recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS). Out of 853 enrolled patients, 783 (91.8%) and 70 (8.2%) had PUC and SUC, respectively. SUC presence was significantly associated with old age, tumor size (≥3cm), higher pT1 rate, high grade, concomitant carcinoma in situ, and lymphovascular invasion. RFS rates after TURBT did not significantly differ between the PUC and SUC groups. With a median follow-up period of 66months (interquartile range, 38-103months), the rates and median time of progression to muscle invasion were 6.9% and 22.5months in the PUC group, and 22.9% and 10.0months in the SUC group. Moreover, the incidence of progression to metastasis was 4.6% and 15.7% in the PUC and SUC groups, respectively. The 5-year PFS rates (64.5% and 81.9%, P< .001) and 5-year OS rates (71.7% and 86.2%, P=.009) were lower in the SUC group than in the PUC group. On multivariate analysis, SUC presence independently predicted progression to muscle invasion and metastasis. At initial TURBT diagnosis, we must pay more attention to higher progression risk of SUC than that of PUC in nonmuscle-invasive bladder cancer.

LGG-38. UNRESECTABLE PEDIATRIC LOW-GRADE GLIOMAS OF THE BRAIN: TARGETED THERAPY COMPARED WITH STANDARD CHEMOTHERAPY AS FIRST-LINE TREATMENT

Abstract BACKGROUND Pediatric low-grade gliomas (pLGG) frequently harbor MAPK-pathway mutations that determine poor response to standard chemotherapy (sCt). Targeted agents against BRAF-V600E mutation (MAPK-i) are emerging as molecularly driven treatments. Few studies have compared sCt with MAPK-i. We aimed to compare response and progression-free survival (PFS) of unresectable brain pLGG treated with sCt or MAPK-i. MAPK-i were used in first line or at relapse. METHODS We conducted a single-center observational retrospective study of all brain pLGG consecutively diagnosed and treated at Gaslini Children’s Hospital between January 2008 and December 2021. Treatment was assessed using RAPNO criteria at 6, 12-18 months, and at last follow-up. MRI studies were reviewed by two experienced neuroradiologists. RESULTS Seventy-one patients were enrolled: 66 received sCt and 10 MAPK-i (5 in first line, 5 after sCt failure). All patients who received MAPK-i were BRAF-V600E mutated. Groups were homogeneous for tumor location and dissemination. sCt group was enriched for pilocytic astrocytoma, MAPK-I group for ganglioglioma. sCt patients were younger. SCt lasted 12-18 months, MAPK-i were continuously given. Tumor size reduction was 19.5% at 6 months and 40.5% at 12-18 months for sCt group; 48% at 6 months and 43.5% at 12-18 months for MAPK-i group. SCt determined at least stable disease in 74.2% of patients; 60% of responders reached the best response at 6 months, 40% at 12-18 months. 5y-PFS was 40.3% (median time for progression: 2.5 years). MAPK-i determined at least stable disease in all patients at first evaluation with long-lasting response (median time of follow-up: 5.1 years). CONCLUSIONS In our study sCt was effective in inducing response but prolonged disease control is not always achieved. BRAF-V600E mutated patients upon MAPK-i start gained a rapid disease control with long-lasting response, also if they have been pretreated. Acknowledgement: this study was supported by ARTUCEBA ONLUS.

Presentation of enthesitis-related arthritis and juvenile-onset spondyloarthritis: a cross-sectional study in a pediatric and adult clinic

BackgroundJuvenile idiopathic arthritis (JIA) comprises a whole spectrum of chronic arthritis starting before 16 years of age. The study aims to explore the clinical and demographic descriptors, treatment, and disease progression of enthesitis-related arthritis (ERA) in comparison with juvenile-onset spondyloarthritis (SpA).MethodsCross-sectional analysis of consecutive patients in two dedicated clinics, with a single visit and retrospective case-notes review. Arthritis, enthesitis and sacroiliitis were evaluated by scoring disease activity and damage. Continuous variables were reported by median, interquartile range; categorical variables were reported by the frequency comparison of the two groups.ResultsThirty-three cases were included, being 23 (69.7%) with ERA. The median age at diagnosis was 12.5 y (SpA) vs. 9 y (ERA) (p < 0.01); the time from symptom onset to diagnosis was 5.5 y (SpA) vs. 1.5 y (ERA) (p < 0.03). In both groups, the predominant presentation was a single joint or < 5 lower limb joints and asymmetric involvement, with a high frequency of enthesitis. There was a higher frequency of mid-tarsal and ankle synovitis in the ERA group and hip involvement in those with SpA. The comparison of the frequency of spine symptoms at presentation, 30% SpA vs. 21.7% ERA (p = 0.7), was not significant, and radiographic progression to spinal involvement occurred in 43.5% of ERA patients. The median time for spinal progression and age at onset was 2.2 and 12 y for ERA, and 4 and 16.5 y for SpA, respectively. Activity and damage scores were not significantly different between the groups. Treatment comparison resulted in 91.3% of ERA and 100% SpA being treated, predominantly with NSAIDs in both groups, followed by DMARDs and biologics, with a higher frequency of biologics in SpA.ConclusionThe main differences were the late diagnoses of SpA, and the hip and spine involvement, with higher frequency of biologic treatment in juvenile-onset SpA compared to ERA.

Assessment of disease control rate and safety of sorafenib in targeted therapy for advanced liver cancer

ObjectiveThe clinical efficacy and safety of sorafenib in patients with advanced liver cancer (ALC) were evaluated based on transarterial chemoembolization (TACE).Methods92 patients with ALC admitted to our hospital from May 2020 to August 2022 were randomly rolled into a control (Ctrl) group and an observation (Obs) group, with 46 patients in each. Patients in the Ctrl group received TACE treatment, while those in the Obs group received sorafenib molecular targeted therapy (SMTT) on the basis of the treatment strategy in the Ctrl group (400 mg/dose, twice daily, followed by a 4-week follow-up observation). Clinical efficacy, disease control rate (DCR), survival time (ST), immune indicators (CD3+, CD4+, CD4+/CD8+), and adverse reactions (ARs) (including mild fatigue, liver pain, hand-foot syndrome (HFS), diarrhea, and fever) were compared for patients in different groups after different treatments.Resultsthe DCR in the Obs group (90%) was greatly higher to that in the Ctrl group (78%), showing an obvious difference (P < 0.05). The median ST in the Obs group was obviously longer and the median disease progression time (DPT) was shorter, exhibiting great differences with those in the Ctrl group (P < 0.05). Moreover, no great difference was observed in laboratory indicators between patients in various groups (P > 0.05). After treatment, the Obs group exhibited better levels in all indicators. Furthermore, the incidence of ARs in the Obs group was lower and exhibited a sharp difference with that in the Ctrl group (P < 0.05).ConclusionSMTT had demonstrated good efficacy in patients with ALC, improving the DCR, enhancing the immune response of the body, and reducing the incidence of ARs, thereby promoting the disease outcome. Therefore, it was a treatment method worthy of promotion and application.

Analysis of risk factors for post-operative recurrence or progression of intravenous leiomyomatosis

ObjectiveTo analyse the risk factors for post-operative recurrence or progression of intravenous leiomyomatosis and explore the impact of different treatment strategies on patient prognosis.MethodsPatients with intravenous leiomyomatosis who underwent surgery...

Who Progresses to Third-Line Therapies for Overactive Bladder? Trends From the AQUA Registry.

Overactive bladder (OAB) patients who do not achieve satisfactory results with second-line OAB medications should be offered third-line therapies (percutaneous tibial nerve stimulation, sacral neuromodulation, onabotulinumtoxinA bladder injection [BTX-A]). We aimed to determine which clinical factors affect progression from second- to third-line OAB therapy. Between 2014 and 2020, the AUA Quality Registry was queried for adult patients with idiopathic OAB. For the primary outcome, patient and provider factors associated with increased odds of progression from second- to third-line therapy were assessed. Secondary outcomes included median time for progression to third-line therapy and third-line therapy utilization across subgroups. A total of 641,122 patients met inclusion criteria and were included in analysis. Of these, only 7487 (1.2%) received third-line therapy after receiving second-line therapy. On multivariate analysis, patients aged 65 to 79, women, White race, history of dual anticholinergic and β3 agonist therapy, metropolitan area, government insurance, and single specialty practice had the greatest odds of progressing to third-line therapy. Black and Asian race, male gender, and rural setting had lower odds of progressing to third-line therapy. BTX-A was the most common therapy overall (40% BTX-A, 32% sacral neuromodulation, 28% percutaneous tibial nerve stimulation). The median time of progression from second- to third-line therapy was 15.4 months (IQR 5.9, 32.4). Patients < 50 years old and women progressed fastest to third-line therapy. Very few patients received third-line therapies, and the time to progression from second- to third-line therapies is > 1 year. The study findings highlight a potential need to improve third-line therapy implementation.

485. MATTHEW EFFECT OF NEOADJUVANT THERAPY IN ESOPHAGEAL CANCER

Abstract Carcinoma. Background Neoadjuvant therapy benefits long-term survival to patients with locally advanced Esophageal Squamous Cell Carcinoma (ESCC). If the survival benefit brought by neoadjuvant therapy is considered as a positive improvement for majority patients, outweighing the negative harms, it means that some patients will experience a reduction in survival due to the negative harms, just as the Matthew effect. This study focuses on these failures of Matthew effect who may not benefit from neoadjuvant therapy and explores the specific recurrent patterns. Method A total of 457 recurrent ESCC patients undergoing curative esophagectomy were enrolled, including 140 patients treated with neoadjuvant therapy. The median progression time (MPT) were 24.3 months. Tumor recurrences or metastases occurring before MPT were defined as treatment failure. We retrospectively investigated the patterns of recurrence and the prognosis in patients with neoadjuvant therapy. Results Among recurrent patients, locoregional recurrence, lung and bone metastases were the most common recurrence sites. The median progression time to the first recurrence was 24.3 months. The locoregional recurrence rate of neoadjuvant group was lower than that of none-adjuvant group (46% vs 60.2%), while the liver and brain metastasis rates was higher (16% vs 7.5% and 8.1% vs 3.3% respectively). Kaplan–Meier analysis showed unsatisfactory prognosis for neoadjuvant therapy failures than those without neoadjuvant therapy. Moreover, for non-neoadjuvant ESCC, shorter overall survival was found in distant recurrence failures than those with locoregional recurrence, while the different recurrence patterns shared similar prognosis for neoadjuvant therapy failures. Conclusion For treatment failure patients with early progression, neoadjuvant therapy has an advantage in controlling local recurrence, but this positive improvement does not transform into survival benefits, indicating Matthew effect of neoadjuvant therapy in ESCC.

Transfusion-dependent non-severe aplastic anemia: characteristics and outcomes in the clinic.

Transfusion-dependent non-severe aplastic anemia (TD-NSAA) is a rare condition of bone marrow failure that can persist for a long time or develop into severe aplastic anemia (SAA). Little is known about the clinical and laboratory characteristics, and disease prognosis and outcomes in TD-NSAA patients. The clinical and laboratory data of 124 consecutive TD-NSAA patients in the Chinese Eastern Collaboration Group of Anemia from December 2013 and January 2017 were analyzed retrospectively. In 124 TD-NSAA patients, the median age was 32 years (range: 3-80) and the median disease course was 38 months (range: 3-363). Common complications were iron overload (53/101, 52.5%), liver and kidney dysfunction (42/124, 33.9%), diabetes mellitus/impaired glucose tolerance (24/124, 19.4%), and severe infection (29 cases, 23.4%). 58% of patients (57/124) developed severe aplastic anemia with a median progression time of 24 months (range: 3-216). Patients with absolute neutrophil count (ANC) <0.5×109/L, severe infection, or iron overload had a higher probability of progression to SAA (P=0.022, P=0.025, P=0.001). Patients receiving antithymocyte globulin (ATG) plus Cyclosporin A (CsA) had a higher overall response rate compared to those receiving CsA alone (56.7% vs 19.3%, P < 0.001). The addition of ATG was the favorable factor for efficacy (P=0.003). Fourteen patients developed secondary clonal hematologic disease: eleven patients with paroxysmal nocturnal hemoglobinuria, two patients with myelodysplastic syndromes, and one patient with acute myeloid leukemia, respectively. Ten patients (8.1%) died with a median follow-up of 12 months (range: 3- 36 months). Patients with TD-NSAA usually have a prolonged course of disease, and are prone to be complicated with important organ damage and disease progression to SAA. Intensive immunosuppressive therapy based on ATG might be an appropriate approach for TD-NSAA. Clinical trial registration: http://www.chictr.org.cn/edit.aspx?pid=125480&htm=4, identifier ChiCTR2100045895.

Surveillance for malignant progression of LI-RADS version 2017 category 3/4 nodules using contrast-enhanced ultrasound.

To identify the risk factors for predicting the malignant progression of LR-3/4 observations on the baseline and contrast-enhanced ultrasound (CEUS). In total, 245 liver nodules assigned to LR-3/4 in 192 patients from January 2010 to December 2016 were followed up by baseline US and CEUS. The differences in the rate and time of progression to hepatocellular carcinoma (HCC) among subcategories (defined as P1-P7) of LR-3/4 in CEUS Liver Imaging Reporting and Data System (LI-RADS) were analyzed. The risk factors to predict progression to HCC were analyzed by univariate and multivariate Cox proportional hazard model analysis. A total of 40.3% of LR-3 nodules and 78.9% of LR-4 nodules eventually progressed to HCC. The cumulative incidence of progression was significantly higher for LR-4 than LR-3 (p < 0.001). The rate of progression was 81.2% in nodules with arterial phase hyperenhancement (APHE), 64.7% in nodules with late and mild washout, and 100% in nodules with both characteristics. The overall progression rate and median progression time of subcategory P1 nodules (LR-3a) were lower (38.0% vs. 47.6-100.0%) and later (25.1months vs. 2.0-16.3months) than those of other subcategories. The cumulative incidence of progression of LR-3a (P1), LR-3b (P2/3/4), and LR-4 (P5/6/7) categories were 38.0%, 52.9%, and 78.9%. The risk factors of HCC progression were Visualization score B/C, CEUS characteristics (APHE, washout), LR-4 classification, echo changes, and definite growth. CEUS is a useful surveillance tool for nodules at risk of HCC. CEUS characteristics, LI-RADS classification, and changes in nodules provide useful information for the progress of LR-3/4 nodules. CEUS characteristics, LI-RADS classification, and nodule changes provide important predictions for LR-3/4 nodule progression to HCC, which may stratify the risk of malignant progression to provide a more optimized and refined, more cost-effective, and time-efficient management strategy for patients. • CEUS is a useful surveillance tool for nodules at risk of HCC, CEUS LI-RADS successfully stratified the risks that progress to HCC. • CEUS characteristics, LI-RADS classification, and changes in nodules can provide important information on the progression of LR-3/4 nodules, which may be helpful for a more optimized and refined management strategy.

The effectiveness of omega-3 fatty acids on health outcomes in women with breast cancer: A systematic review.

This study aimed to systematically evaluate the impact of omega-3 fatty acids on the health outcomes of women with breast cancer in electronic databases (PubMed, Scopus, ProQuest, Web of Science, and Cochrane Library) for interventional studies. The risk of bias and the quality of the included articles were assessed by Cochrane Collaboration Handbook guidance. The statistical analyses were not conducted because of the heterogeneity of the included studies. Of 3676 identified articles, 11 articles were included in this study. The majority of the included studies were not of high quality. Median progression time and overall survival significantly improved. Additionally, surgical site healing complications and infection rates decreased. There was a significant decrease in perceived stress, sleep disturbance, depression, pain, joint stiffness, and fatigue throughout the intervention. Moreover, omega-3 fatty acids consumption significantly increased the total serum omega-3, EPA, and DHA, and decreased the omega-6: omega-3 ratio, total leukocytes, lymphocytes, leptin, and CRP, accordingly. Mild gastrointestinal symptoms were reported in only two studies without clinically relevant adverse events. Omega-3 fatty acids may cause improvement in physical, mental, and some inflammatory and metabolic indices during treatment or posttreatment course of breast cancer patients. Due to the possibility of free radical formation, omega-3 FAs supplementation and consumption must be done very carefully.

P790: THE EXPRESSION LEVEL OF WT1 MRNA IN PATIENTS WITH IDIOPATHIC CYTOPENIA OF UNDETERMINED SIGNIFICANCE (ICUS) PROGRESSING TO MYELODYSPLASTIC SYNDROME (MDS)

Background: Idiopathic cytopenia of undetermined significance (ICUS) is defined as patients with one or more unexplained cytopenia who do not meet diagnostic criteria for myelodysplastic syndrome (MDS) or another hematologic disorder. In the clinical course of ICUS, some patients eventually have typical MDS changes. Until now, there is no effective method to predict the development of the disease. Recent studies have shown that the expression level of WT1 mRNA in peripheral blood has important clinical significance in the diagnosis, occurrence, development and prognosis of MDS. At the same time, some studies have proved that there is a significant difference in the expression level of WT1 mRNA between MDS and hemocytopenia caused by other reasons. Aims: In order to clarify the clinical significance of WT1 mRNA expression in the progression of ICUS to MDS. Methods: Between April 2017 and January 2020, untreated adult patients with ICUS or lower-risk MDS were enrolled in the study. All patients detected the WT1 mRNA expression of bone marrow and peripheral blood at diagnosis. Then patients with ICUS were followed up. Every three months, the patients with ICUS detected the WT1 mRNA expression of peripheral blood, until the patient progressed to MDS. The results of WT1 transcript levels are depicted as WT1 (copies/mL)/c-ABL (copies/mL) as a percentage. Results: Total of 80 patients with ICUS and 40 patients with lower-risk MDS were enrolled. At diagnosis, the median expression level of WT1 mRNA in MDS group was 5.99 (0.08-79.27), and that in ICUS group was 0.50 (0.16-22.48). There was significant difference between them (P = 0.000). Then 80 patients with ICUS were followed up to January 2022. The median follow-up time was 30 months (11-54 months). 8 patients developed MDS, the progression rate was 10%, and the median progression time was 6.5 months (2-19 months). The median expression level of WT1 mRNA at the initial diagnosis in ICUS group without progressing to MDS was 0.44 (0.16-7.58), and that in progressing to MDS group was 9.44 (0.26-22.48). There was significant difference between the two groups (P = 0.031). The median expression level of WT1 mRNA was 19.185 (0.73-42.30) when MDS was diagnosed. The median maximum expression level of WT1 mRNA in peripheral blood of ICUS group without MDS was 0.98 (0.22-7.58). There was significant difference between the two groups (P = 0.007). Summary/Conclusion: The study clarified the WT1 mRNA expression status of ICUS patients. There were significant differences in WT1 mRNA expression level between patients with ICUS and lower-risk MDS, and the WT1 mRNA expression level of patients with lower-risk MDS was relatively high. The study confirmed that patients with high WT1 mRNA expression level in the patients with ICUS (WT1 mRNA expression level > 9.44) are very likely to progressing to MDS; Dynamic monitoring of WT1 mRNA expression in peripheral blood is an effective method for following-up after ICUS diagnosis. The progressive increase of WT1 mRNA expression is one of the indicators for researchers to judge the progress of ICUS to MDS.

The emerging postural instability phenotype in idiopathic Parkinson disease

Identification of individuals at high risk for rapid progression of motor and cognitive signs in Parkinson disease (PD) is clinically significant. Postural instability and gait dysfunction (PIGD) are associated with greater motor and cognitive deterioration. We examined the relationship between baseline clinical factors and the development of postural instability using 5-year longitudinal de-novo idiopathic data (n = 301) from the Parkinson’s Progressive Markers Initiative (PPMI). Logistic regression analysis revealed baseline features associated with future postural instability, and we designated this cohort the emerging postural instability (ePI) phenotype. We evaluated the resulting ePI phenotype rating scale validity in two held-out populations which showed a significantly higher risk of postural instability. Emerging PI phenotype was identified before onset of postural instability in 289 of 301 paired comparisons, with a median progression time of 972 days. Baseline cognitive performance was similar but declined more rapidly in ePI phenotype. We provide an ePI phenotype rating scale (ePIRS) for evaluation of individual risk at baseline for progression to postural instability.

The Dynamics of Nucleotide Variants in the Progression from Low-Intermediate Myeloma Precursor Conditions to Multiple Myeloma: Studying Serial Samples with a Targeted Sequencing Approach.

Simple SummaryMultiple myeloma (MM), characterized by the expansion of plasma cells in the bone marrow, is the second most common hematological malignancy. This incurable cancer is consistently preceded by non-malignant asymptomatic precursor conditions known as monoclonal gammopathy of undetermined significance (MGUS) and/or smoldering multiple myeloma (SMM). These pre-stages are relatively frequent, but only a select percentage of them will progress to MM. However, it is still not possible to individually predict when and which patients will develop MM. Therefore, this study aimed to investigate the mutational profile in the progression in serial bone marrow samples with a custom targeted sequencing panel, designed to detect variants in myeloma-related genes. Remarkably, almost all variants identified in the MM samples were also already present in the pre-stages, sometimes even many years before the progression. These results provide new important insights into the molecular mechanisms of the precursor conditions and progression to MM.Multiple myeloma (MM), or Kahler’s disease, is an incurable plasma cell (PC) cancer in the bone marrow (BM). This malignancy is preceded by one or more asymptomatic precursor conditions, monoclonal gammopathy of undetermined significance (MGUS) and/or smoldering multiple myeloma (SMM). The molecular mechanisms and exact cause of this progression are still not completely understood. In this study, the mutational profile underlying the progression from low–intermediate risk myeloma precursor conditions to MM was studied in serial BM smears. A custom capture-based sequencing platform was developed, including 81 myeloma-related genes. The clonal evolution of single nucleotide variants and short insertions and deletions was studied in serial BM smears from 21 progressed precursor patients with a median time of progression of six years. From the 21 patients, four patients had no variation in one of the 81 studied genes. Interestingly, in 16 of the 17 other patients, at least one variant present in MM was also detected in its precursor BM, even years before progression. Here, the variants were present in the pre-stage at a median of 62 months before progression to MM. Studying these paired BM samples contributes to the knowledge of the evolutionary genetic landscape and provides additional insight into the mutational behavior of mutant clones over time throughout progression.

Radiologic-pathologic correlation of interstitial lung abnormalities and predictors for progression and survival.

To evaluate radiologic and histologic correlations for interstitial lung abnormalities (ILAs) and to investigate radiologic or pathologic features contributing to disease progression and mortality. From 268 patients who underwent surgical lung biopsy between January 2004 and April 2019, 45 patients with incidentally detected ILA and normal pulmonary function were retrospectively included. CT features were classified as subpleural fibrotic or non-fibrotic, and changes in ILA over at least 2 years of follow-up were evaluated. Histologic findings were categorized as definite, probable, indeterminate, or alternative diagnosis for usual interstitial pneumonia (UIP) patterns. Overall and progression-free survival were calculated using the Kaplan-Meier method, and the Cox proportional hazard method was used to examine predictors for ILA progression and survival. Among 36 subpleural fibrotic ILA subjects, 25 (69%) showed definite or probable UIP patterns, and 89% (8/9) of subpleural non-fibrotic ILA subjects showed an indeterminate or alternative diagnosis for UIP pattern on histopathology. On the radiologic-pathologic correlation, reticular opacity of fibrotic ILA was correlated with patchy involvement of fibrosis, and ground-glass attenuation of non-fibrotic ILA corresponded to diffuse interstitial thickening. The median progression time of ILA was 54 months, and fibrotic ILA increased the likelihood of progression (hazard ratio, 2.42; p= 0.017). The median survival time of ILA subjects was 123 months, and fibrotic ILA was associated with an increased risk of death (hazard ratio, 9.22; p = 0.025). Subpleural fibrotic ILAs are associated with pathologic UIP patterns, and it is important to recognize subpleural fibrotic ILA on CT to predict disease progression and mortality. • In total, 69% of subpleural fibrotic ILA showed definite or probable UIP patterns, while 11% of subpleural non-fibrotic ILA showed definite or probable UIP patterns. • Subpleural fibrotic ILA was associated with an increased rate of progression (hazard ratio, 2.42; p= 0.017), and the median progression-free time was 40 months. • Subpleural fibrotic ILA had an increased risk of death (hazard ratio, 9.22; p = 0.025), and the median survival time was 86 months.

The efficacy and safety of pyrotinib in treating HER2-positive breast cancer patients with brain metastasis: A multicenter study.

PurposeTo investigate the efficacy and safety of pyrotinib in treating patients with human epidermal growth factor receptor type 2 (HER2)‐positive breast cancers with brain metastasis.Patients and MethodsThis is a multicenter retrospective study, and the HER2‐positive breast cancer patients with brain metastasis were studied. The enrolled patients were given pyrotinib 400 mg orally once per day for 21 days as one cycle, and evaluated every two cycles. All relevant data were detected for final assessments including medical history, clinical examination, histopathology, immunohistochemistry, radiographic imaging, treatment outcome, and adverse events.ResultsForty‐two female patients in total were enrolled in this study. The objective response rate (ORR) and disease control rate (DCR) of central nervous system (CNS), were found in 20 of 42 (47.6%) and in 39 of 42 (92.8%), respectively, while for extra‐CNS, the respective ORR and DCR were in 9 of 38 (23.6%) and in 36 of 38 (94.7%), respectively. The compounded ORR and DCR were seen in 17 of 42 (40.4%) and in 39 of 42 (92.8%), respectively. The improvement rate of craniocerebral symptoms after treatment was (19/19) 100% and the median duration was 15 months. The median effective time of brain metastases and other metastases was 43 and 50 days. The median follow‐up time was 22 months (interquartile range, 16.0–24.3 months). The median time for progression in brain metastasis was 16.6 months. The median time to progress for our group patients was 11.1 months. Sixteen patients (36%) with adverse reactions were recorded in the study.ConclusionPyrotinib combined with chemotherapy/radiotherapy or alone showed significantly greater local control rates and progression free survival (PFS), with manageable toxicity for patients with HER2‐positive breast cancer with brain metastases, and further follow‐up will provide an overall survival (OS) data.

Oligoblastic (

Introduction: The current World Health Organization (WHO) classification considers acute myeloid leukemia (AML) with PML-RARA, RUNX1-RUNX1T1, and CBFB-MYH11 to be AML regardless of blast count. Myeloid neoplasms with KMT2A rearrangement present with high blast percentages and are classified as AML in the vast majority of cases; however, rare myeloid neoplasms with KMT2A rearrangement may present with <20% blasts and these are currently considered to be myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML). We questioned whether these oligoblastic KMT2A rearranged neoplasms shared similar biology with AML, and if this genetic finding should be considered to be AML-defining.Methods: We searched the archives of three large institutions in the United States for untreated adult with oligoblastic (<20%) myeloid neoplasms with KMT2A rearrangement and untreated adult AML patients with KMT2A rearrangement and compared their clinical and laboratory characteristics. KMT2A rearrangement was detected by chromosomal analysis and/or fluorescence in-situ hybridization (FISH) using KMT2A breakapart probe. KMT2A rearrangement partners were assessed based on a conventional karyotype results and/or RNA based fusion assay.Results: Between 2010 and 2021 we identified 22 patients with MDS or CMML and KMT2A rearrangement and 88 patients with AML and KMT2A rearrangement. The clinical and laboratory information are summarized below. MDS/CMML with KMT2A-rearrangement showed a similar age and sex distribution to AML, but had more patients with preceding history of chemotherapy for unrelated malignancies (68% vs 37%, p=0.012). Aside from a low blast count in PB and BM, patients with MDS/CMML had a lower WBC and were less anemic and thrombocytopenic. MDS/CMML patients also showed a lower percentage of BM cells with KMT2A rearrangement by FISH (58% vs. 92%, p<0.0001), and significantly less likely to have MLLT3 as the partner gene (23% vs. 58%, p=0.0005). With a similar mutation frequency among patients tested (42% versus 34%, p=0.22), MDS/CMML patients had significantly fewer mutations involving the RAS pathway (KRAS, NRAS, FLT3, PTPN11) than AML patients (p=0.0035).Seventeen of 22 MDS/CMML patients (77%) progressed to AML with a median time of progression being 4 months (range, 1-27 months). Of the 5 patients who did not progress to AML, 3 received allogeneic stem cell transplantation (SCT) and remain in complete remission, while 2 remain AML-free 3 and 16 months after the initial diagnosis.With a median follow-up of 12 months (range, <1-117), 15 MDS/CMML patients and 58 AML patients died. There was no difference in use of SCT to treat MDS/CMML versus AML (p=0.47). MDS/CMML and AML patients displayed similar overall survival (OS) (p=0.9059, Figure 1). There was also no statistical difference in OS between MDS/CMML and AML when therapy-related (p=0.569) and de novo (p=0.962) neoplasms were analyzed separately. On multivariable analysis, therapy-related disease (HR 1.774 [1.058-2.975], p=0.03), SCT (HR 0.166 [0.000-0.291], p<0.0001), and platelet count (HR 0.992 [0.000-0.998], p=0.013) were independently associated with shorter OS. Neither AML versus MDS/CMML nor blast percentage (whether dichotomized as <5% or >=5% or as a continuous variable) were associated with shorter OS.Conclusion: Oligoblastic myeloid neoplasms with KMT2A rearrangement tend to progress rapidly to overt AML and demonstrate similar aggressive behavior to AML patients with KMT2A rearrangement, irrespective of therapy relatedness. Patients with KMT2A rearrangement and <20% blasts are currently classified as MDS or CMML, and may be inadequately treated. Our findings suggest that all myeloid neoplasms with KMT2A (MLL) rearrangement should be classified as AML, irrespective of the blast count. [Display omitted] DisclosuresRavandi: AbbVie: Honoraria, Research Funding; Prelude: Research Funding; Taiho: Honoraria, Research Funding; Xencor: Honoraria, Research Funding; Astex: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Jazz: Honoraria, Research Funding; Agios: Honoraria, Research Funding; Novartis: Honoraria; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Syros Pharmaceuticals: Consultancy, Honoraria, Research Funding. Issa: Novartis: Consultancy, Research Funding; Kura Oncology: Consultancy, Research Funding; Syndax Pharmaceuticals: Research Funding. Pozdnyakova: Scopio Labs: Consultancy. Wang: Stemline Therapeutics: Honoraria.

CT-guided microwave ablation in patients with lung metastases from breast cancer.

BackgroundComputed tomography (CT)‐guided percutaneous microwave ablation (MWA) is a very common ablation method that shows a good local tumor control rate in primary and secondary lung tumors. At present, few reports have explored the safety and efficacy of MWA for lung metastases from breast cancer.MethodsFrom January 2012 to January 2018, 32 breast cancer patients with 46 pulmonary metastases received CT‐guided percutaneous MWA. The study was approved by the local institutional review board. The clinical efficacy and complications of MWA were investigated.ResultsThe median follow‐up time was 32 months and the main effective rate was 97.8% (45/46). Five of 46 lesions had local progression (10.9%), with a median progression time of 10 months. The 1‐, 3‐, and 5‐year overall survival (OS) rates were 96.9%, 53.3%, and 17.8%, respectively. The median OS time was 36 months. Among 46 MWA treatments, 11 (23.9%) had massive pneumothorax, two (4.3%) had massive pleural effusion, and two (4.3%) had a pulmonary infection.ConclusionCT‐guided percutaneous MWA may be safe and effective for treating lung metastases from breast cancer.

Initial Experience of Drug-Eluting Bead-Transcatheter Arterial Chemoembolization After Lipiodol-Based Transcatheter Arterial Chemoembolization Failure for Patients with Advanced Hepatocellular Carcinoma.

PurposeTo investigate the potential safety and efficacy of drug-eluting bead-transcatheter arterial chemoembolization (DEB-TACE) in treating TACE-refractory hepatocellular carcinoma (HCC).MethodsWe retrospectively evaluated the treatment outcomes of DEB-TACE for 41 HCC nodules in 30 patients who were refractory to conventional TACE (c-TACE) according to tumor response. The antitumor response was evaluated according to mRECIST criteria, and changes in alpha-fetoprotein (AFP), albumin-bilirubin score, the incidence of adverse events, and the time to disease progression were observed.ResultsThe objective response rate and disease control rates were 60.98% and 95.12% at 4 weeks after DEB-TACE, 63.41% and 92.68% at 8 weeks, respectively. The median time of disease progression was 4.60 ± 0.23 months. The AFP of patients decreased continuously at 2–6 weeks after operation, and the AFP at 4 weeks was significantly lower than that at 2 weeks (P = 0.038). Adverse reactions were well tolerated, and no grade 4 adverse reactions were reported. The albumin-bilirubin score did not deteriorate within 6 weeks.ConclusionDEB-TACE has potential efficacy and safety after failure of c-TACE in patients with advanced liver cancer. Further studies are needed to confirm the efficacy of DEB-TACE treatment after failure of c-TACE.

Patterns of Failure in Patients With Advanced Non-Small Cell Lung Cancer Treated With Immune Checkpoint Inhibitors

ObjectiveThe advent of immune checkpoint inhibitors (ICIs) has rapidly transformed the treatment paradigm of non-small cell lung cancer (NSCLC). Despite the durability of response to ICIs, the vast majority of patients will later develop progression. However, the failure patterns of ICI treatment are unknown. Here, our study explored the failure patterns in advanced NSCLC patients treated with ICIs.MethodsA cohort of 156 IIIB or IV NSCLC patients treated with first-/second-line ICIs were retrospectively analyzed. Patients who experienced clinical benefit and then developed progression were identified. The disease progression patterns were divided into three categories: progression in new sites, progression in existing sites, and combined progression. The number of progression sites was also recorded.ResultsBefore the cutoff date, 91 (77.1%) patients had experienced disease progression; 34% of patients had progressed in the last 9 months of the first year. Fifty-three (58.2%) patients had developed progression at existing lesions, and 56 (61.5%) patients had shown ≤2 progression sites (oligo-progression). In patients with oligo-progression, the median time of disease progression was 8.23 months and the counterpart (systemic progression) was 5.97 months. The oligo-progression patients showed prolonged median overall survival (27.23 months) compared with patients with systemic progression (18.87 months).ConclusionsFailure patterns of ICI therapy were predominantly “existing” sites, and the most common lesions of progression were the lung and lymph nodes. Most patients experienced oligo-progression which occurred later than systemic progression and showed prolonged overall survival. The control of the local lesions might be beneficial to improve ICI treatment efficacy.