Overall Survival Time Research Articles

Prognosis of immunotherapy for non-small cell lung cancer with CDKN2A loss of function.

Immunotherapy has been widely used to treat non-small cell lung cancer (NSCLC) but is only effective in 20% of patients. Cyclin-dependent kinase inhibitor 2A (CDKN2A) is an important tumor suppressor gene, and its loss of function (LOF) is quite common in NSCLC. Pre-clinical studies suggest CDKN2A LOF promotes immune evasion; however, the results in relation to NSCLC are controversial, and debate continues as to the effect of CDKN2A LOF on immunotherapy. In this study, we collected the data of 49 CDKN2A LOF and 173 CDKN2A wild-type NSCLC consecutive patients treated by any line of immunotherapy. Through immunohistochemical (IHC) and immunofluorescent (IF) staining, we analyzed the CDKN2A predominant transcription protein p16INK4A in the CDKN2A LOF and CDKN2A wild-type NSCLC patients. Using Kaplan-Meier curves, we also examined the relationship between CDKN2A LOF and immunotherapy. The IHC and IF staining results showed that most CDKN2A LOF patients were p16INK4A negative, while most CDKN2A wild-type patients were p16INK4A positive. In the LOF group, five patients had partial responses, 35 had stable disease, and nine had progressive disease after the first evaluation of immunotherapy. The LOF group had a median progression-free survival (PFS) time of 4.67 months, while the wild-type group had a median PFS time of 8.63 months [hazard ratio (HR): 0.54; 95% confidence interval (CI): 0.38-0.77; P<0.001]. The LOF group had a median overall survival (OS) time of 9.07 months, while the wild-type group had a median OS time of 21.37 months (HR: 0.42; 95% CI: 0.29-0.61; P<0.001). Our study revealed that CDKN2A LOF NSCLC patients treated with immune checkpoint inhibitor (ICI) mono-therapy or combined therapy had a worse prognosis than those with CDKN2A wild-type NSCLC. However, our study also suggested that ICI could work quite effectively in selective CDKN2A LOF patients.

Efficacy and safety of lenvatinib plus pembrolizumab in patients with advanced and recurrent endometrial cancer: a systematic review and meta-analysis.

Various trials have demonstrated the clinical benefits of lenvatinib plus pembrolizumab in patients with advanced or recurrent endometrial cancer, regardless of mismatch repair (MMR) status or histologic subtype. The majority of the previously published trials had small sample sizes. Here, we aimed to assess the reported efficacy and safety profile of lenvatinib plus pembrolizumab in patients with advanced and recurrent endometrial cancer. We utilized the Cochrane Library, PubMed, Web of Science and Embase databases to identify clinical trials evaluating the efficacy and safety of lenvatinib plus pembrolizumab in patients with advanced and recurrent endometrial cancer. The outcomes analyzed were progression-free survival (PFS), overall survival (OS), the objective response rate (ORR), the disease control rate (DCR) and the incidence of adverse events (AEs). Subgroup analysis was conducted on the basis of MMR status (deficient, dMMR or proficient, pMMR). Four trials (582 patients) were included. The pooled ORR was 32.7% [95% confidence interval (CI): 28.9-36.5]. Subgroup analysis revealed an ORR of 48.1% (95% CI: 26.1-70.2) for dMMR group and 33.1% (95% CI: 25.7-40.6) for pMMR group. The pooled DCR was 74.9% (95% CI: 71.3-78.4%). Subgroup analysis revealed a DCR of 81.0% (95% CI: 64.5-97.6) for the dMMR group and 76.3% (95% CI: 66.3-86.3) for the pMMR group. Follow-up was reported in all included studies. The median range time of PFS and OS was 5.3 months-258 days and 17.2 months-not reached, respectively. Regarding safety, the overall pooled proportions of any-grade AE and AEs ≥ grade 3 were 95.8% (95% CI: 89.5-100.0) and 80.2% (95% CI: 59.9-100.0), respectively. Lenvatinib plus pembrolizumab showed a relevant clinical benefit and significant toxicity in patients with advanced and recurrent endometrial cancer. Further studies encompassing long-term outcomes are warranted. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=522160/, identifier CRD42024522160.

Survival Analysis of Triple Negative Breast Cancer Patients Based on Ki-67 Protein Expression in Prof. Dr. I.G.N.G Ngoerah General Hospital Denpasar

Aim: To prove that 2-year mortality of triple-negative breast cancer (TNBC) patients with protein Ki-67 expression ≥ 40% is higher than patients with protein Ki-67 expression &lt; 40% in Prof. dr. I.G.N.G. Ngoerah General Hospital Denpasar. Methods: This was a bidirectional cohort study with survival analysis. The end of follow-up was the mortality state (survived or deceased) of patients observed for 24 months (2 years) since the patient was diagnosed with TNBC. This study was conducted in the Surgical Oncology Department, Prof. dr. I.G.N.G. Ngoerah General Hospital Denpasar from January 2018 until January 2022. The sample was recruited by a consecutive sampling method. The Kaplan-Meier curve and log-rank test determined overall survival (OS) and its difference between the Ki-67 expression group. Multivariate analysis using Cox regression was also conducted. Results: 58 TNBC patients were included in this study. At the end of the study, 31 patients survived, with an OS of 53.4%. The mean OS time was 19 months (95%CI = 17.12-20.88). The two-year OS of TNBC patients with Ki-67 ≥ 40% group was 37.5%; meanwhile, in Ki-67 expression &lt; 40% was 88.9%. It was statistically significant (p = 0.001). Multivariate analysis revealed that Ki-67 ≥ 40% expression was a significant and independent predictor factor for a high 2-year mortality rate (adjusted HR = 9.140; p = 0.008). Tumor-resection history also had a significant result in multivariate analysis (p &lt; 0.05). Conclusion: TNBC patients with Ki-67 ≥ 40% have a higher 2-year mortality rate than patients with Ki-67 expression &lt; 40%.

Survival Outcomes and Prognostic Factors in Oral Squamous Cell Carcinoma with Locoregional Recurrence: A Retrospective Analysis

Introduction: Recurrence is known to occur in approximately 25% to 45% of patients treated for oral cancer. It is the most common cause of treatment failure in oral squamous cell carcinoma (OSCC), which adversely affects survival. Although recurrences in the oral cavity may be detected early, survival rates remain low. Aim: To identify the survival outcomes and prognostic factors in OSCC with locoregional recurrence. Materials and Methods: This retrospective study was conducted at the Malabar Cancer Centre between November 2020 to March 2021, analysing patients who were treated with curative intent between January 1997 and December 2017. It included 118 patients with OSCC who experienced recurrence-local, regional, or both-after curative treatment. Demographic variables, clinical variables, and follow-up details were analysed. Characteristics of the primary tumour, including nodal metastasis, stage, Extranodal Extension (ENE), Perineural Invasion (PNI), the extent of treatment, adjuvant therapy, and days to recurrence, were recorded. For the recurrent tumour, site, time to recurrence, and type of treatment received were noted additionally. Overall Survival (OS) was defined from the date of initial diagnosis, while the date of recurrence was determined by pathological confirmation. Statistical analysis was performed using SPSS software, version 20. All significant variables (p&lt;0.05) were then tested in a multivariate analysis using Cox regression methods. Disease-specific survival (DSS) and OS were analysed using the Kaplan-Meier method. Results: A total of 146 patients with OSCC (15.01%) experienced a recurrence-local, regional, or both-upon analysis of 973 OSCC patients who underwent primary curative intent surgery. One hundred eighteen patients were included in the final analysis. Salvage surgery was performed on 65 (55.08%) patients. Thirtyeight patients (32.3%) who presented with early-stage disease initially developed a recurrence, whereas recurrences were more common among patients with advanced-stage disease, accounting for 80 (67.7%) cases. The median age of patients with recurrence was 60 years, with a median follow-up period of 46 months. The median OS time for patients with recurrence was 34 months ranging from 26.343 to 42.457 months. Univariate analysis revealed that nodal stage, salvage surgery, and time to recurrence were significant factors affecting OS. On multivariate analysis, salvage surgery and time to recurrence remained significant factors impacting survival. Conclusion: Salvage surgery and time to recurrence were identified as significant prognostic factors affecting survival outcomes in patients with OSCC experiencing locoregional recurrence. Salvage surgery significantly improves survival in oral cancer, where recurrence is usually detected more easily unlike other subsites. Patients with late recurrences demonstrated better survival outcomes. Tumours that recur early indicated poor oncological outcomes, suggesting an aggressive nature. Tumor biology is essential in guiding treatment options in recurrent settings.

Large granular lymphocyte lymphoma in 65 dogs (2005-2023).

Large granular lymphocyte lymphoma (LGLL) is a rare form of lymphoma in dogs. Limited information exists regarding presentation, treatment response, and outcome. The aim of this single-institute, retrospective study was to characterise clinical presentation, biologic behaviour, outcomes, and prognostic factors for dogs with LGLL. Cytologic review was also performed. Sixty-five dogs were included. The most common breed was the Labrador retriever (29.2%), and the most common presenting signs were lethargy (60.0%) and hyporexia (55.4%). The most common primary anatomic forms were hepatosplenic (32.8%) and gastrointestinal (20.7%). Twenty dogs (30.8%) had peripheral blood or bone marrow involvement. Thirty-two dogs were treated with maximum tolerated dose chemotherapy (MTDC) with a response documented in 74.1% of dogs. Dogs ≥7 years, and those with neutropenia or thrombocytopenia at diagnosis had the reduced likelihood of response to treatment. For dogs treated with MTDC median progression-free interval (PFI) was 17 days (range, 0-481), the median overall survival time (OST) 28 days (range, 3-421), and the 6-month and 1-year survival rates were 9.4% and 3.1%, respectively. On multivariable analysis, monocytosis and peripheral blood involvement were significantly associated with shorter PFI and OST. Long-term survival (≥100 days) was significantly associated with intermediate lymphocyte size on cytology. Dogs with LGLL have moderate response rates to chemotherapy but poor overall survival. Additional studies are needed to further evaluate prognostic factors and guide optimum treatment recommendations.

Deep synergetic spiking neural P systems for the overall survival time prediction of glioblastoma patients

Histopathological whole slide images (WSIs) are the gold standard for cancer diagnosis. In prognosis, WSIs can also help predict the overall survival (OS) time of cancer (such as glioblastoma (GBM) patients). However, current region of interest (ROI)-based supervised learning methods for GBM patients are unsatisfactory in accuracy and efficiency. To mitigate the issues, we propose a novel deep synergetic spiking neural (DSSN) P system to perform ROI-free prediction of OS time in GBM patients. Specifically, a dual-task attention network is designed by different synergistic firing mechanisms on new types of neurons to predict OS time and classify genotype simultaneously. The network can not only capture useful cell features but also enrich and share features between the two tasks to improve performance. Four triggering rules are also proposed to cluster pathological images into different phenotypes related to survival to implement ROI-free prediction. Since P systems are highly parallel, multiple preprocessing and ensemble learning of dual-task attention networks with different initial configurations are conducted to further improve OS time prediction accuracy and reduce time complexity. Experimental results show that the DSSN P system outperforms ten other state-of-the-art models, demonstrating the ability of the DSSN P system to predict OS time in GBM patients.

Management and prognosis of patients with cancer of unknown primary: 20 years of experience.

Cancer of unknown primary (CUP) is a difficult clinical entity to manage. The aim of the study was to investigate the sociodemographic and pathological characteristics, treatment options, and factors affecting overall survival (OS) in CUP patients whose primary tumor was not detected during follow-up. A total of 243 CUP patients whose primary tumors could not be detected during follow-up were included in the study. Their demographic characteristics, survival outcomes, and prognostic factors were investigated. Of the 243 patients included in this study, 61.7% were male and 38.3% were female, and the median age was 61 (range: 19-90) years. The most common histological type was adenocarcinoma (79%). The median follow-up time of the patients was 30.3 months (95% CI: 11.4-49.3), the median OS time was 9.1 months (95% CI: 7.2-11.0), and 72.4% of the patients received at least 1 line of chemotherapy (CT). The difference in survival between the patients who did and did not receive CT was statistically significant (median OS: 10.1 vs. 4.2 months, p = 0.003). According to the multivariate analysis, the presence of cholestasis (HR: 0.48, 95% CI: 0.29-0.79, p = 0.004), lung metastasis (HR: 0.69, 95% CI: 0.51-0.95, p = 0.001), second-line chemotherapy (HR: 1.69, 95% CI: 1.14-2.49, p < 0.001), and Eastern Cooperative Oncology Group (ECOG) performance status (HR: 0.20, 95% CI: 0.10-0.40, p < 0.001) were independent prognostic factors influencing OS. CUP patients who receive multiple lines of chemotherapy tend to have longer survival. This is the first study to report cholestasis as a prognostic factor in CUP patients. In addition, the presence of lung metastases, not receiving second-line chemotherapy, and ECOG performance status (≥2) were found to be independent poor prognostic factors.

Proton Beam Therapy for Lung Oligometastatic Recurrence in Patients With Esophageal Cancer.

Local treatment of oligometastatic esophagogastric cancer has been reported to improve overall survival (OS) compared to systemic therapy alone. This study evaluated the feasibility and safety of proton beam therapy (PBT) for the treatment of lung oligometastatic recurrence in esophageal cancer patients. This single-center historical cohort study enrolled 11 patients who underwent PBT for lung oligometastasis from esophageal cancer between 2010 and 2019. The selection criteria were that the primary esophageal cancer was controlled and no more than three lung metastases without outside lung tumors were present. OS, progression-free survival (PFS), and local control (LC) rates and adverse events (AEs) were assessed. Factors that may be related to OS were also investigated. The median follow-up period was 27.8 months (8.8-141.3 months). The one-, two-, and three-year OS rates were 81.8%, 72.7%, and 51.9%, respectively (median OS time: 43.7 months); PFS rates were 45.5%, 27.3%, and 27.3%, respectively (median PFS time: 8.8 months); and LC rates were 92.3%, 72.7%, and 72.7%, respectively. The eighth edition of tumor-node-metastasis (TNM) classification for esophageal cancer was the only significant OS-related factor (p = 0.0309). No grade ≥ 3 AEs were observed. Based on the low incidence of AEs and acceptable LC rate, PBT is a feasible option for the treatment oflung oligometastasis in esophageal cancer patients.

10025-MPC-3 DIFFERENCE AMONG GENERATIONS IN PATIENTS WITH HISTONE H3-MUTATED GLIOMAS

Abstract OBJECT This study investigates clinical and molecular features, including the survival outcomes, of patients with histone H3-mutant gliomas and the differences among generations: children (-13 years), adolescence and young adult (AYA) (14-39 years), and older adult (40- years) patients. Particularly, we focused on the older adult cases. METHODS We collected pediatric and adult glioma cases harboring histone H3 mutations (K27M and G34R/G34V) enrolled in Kansai Network (118 cases) and retrospectively analyzed clinical characteristics and genetic status, including overall survival times (OS). Additionally, the differences between the older adult (40- years) and the younger generations (-39 years) were evaluated. RESULTS The older adult patients were not infrequently enrolled in the H3 K27-mutant glioma group (n = 47) (40-79 years old)), although H3 G34-mutant glioma cases belonged to around AYA generation (11-45 years old). Most popular location was brainstem in children (8/15, 53%) and thalamus in AYA (29/56, 52%), while cerebrum as well as brainstem and thalamus were common in the older adults (15/47, 32%; 15/47, 32%; 11/47, 24%). Histologically, diagnosis of non-GBM was not uncommon (63/105, 60%). There were no significant age-specific differences in genetic status (IDH1/2, TERT promoter, MGMT promoter, TP53, BRAF, FGFR1, EGFR). In general, tumor biopsy followed by radiation and chemotherapy was the main treatment regimen regardless of patient age (92/115, 80%). Particularly in the H3 K27-mutant gliomas, there was no statistically significant difference in OS among generations (median OS of children/AYA/older adult, 16.6/18.4/15.9 months). CONCLUSIONS We report clinicopathological features and survival outcomes of histone H3-mutated glioma patients in Kansai Network cohort. Histone H3 mutation could exist in the older adult cases with diffuse gliomas at cerebral location. There was a little difference in clinical and pathological features among generations. The prognosis of the older adults was as poor as those of children and AYA.

Comprehensive analysis and immunohistochemistry localization of NRP1 expression in pancancer and normal individual tissues in relation to SARS‑CoV‑2 susceptibility.

Neuropilin 1 (NRP1/CD304) is a typical membrane-bound co-receptor for vascular endothelial growth factor, semaphorin family members and viral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, NRP1 expression levels across cancer types and the potential role of SARS-CoV-2 infection in patients with cancer are not clear. Online databases, such as The Cancer Genome Atlas database of Human Protein Atlas, Gene Expression Profiling Interactive Analysis and cBioPortal were used for the expression analysis in this study. Immunohistochemical (IHC) staining for NRP1 was performed in the tissues of patients with non-small cell carcinoma. As a result, it was found that NRP1 mRNA and protein expression levels were highest in the female reproductive tissues and the respiratory system, specifically in the nasopharynx, bronchus and fallopian tube, as well as in adipocytes, hepatic stellate cells, Sertoli cells, endothelial cells and dendritic cells. IHC showed that the NRP1 protein was mainly localized to the cytoplasm and membrane in the tissues of patients with non-small cell carcinoma, demonstrating its role in lung infection by SARS-CoV-2, due to invasion of cell membranes by the virus. Levels of NRP1 mRNA were significantly increased in lymphoid neoplasm diffuse large B-cell lymphoma, esophageal carcinoma, glioblastoma multiforme, head and neck squamous cell carcinoma, kidney renal clear cell carcinoma (KIRC), pancreatic adenocarcinoma, stomach adenocarcinoma and thymoma, and significantly decreased in cervical squamous cell carcinoma and endocervical adenocarcinoma, kidney chromophobe, lung squamous cell carcinoma, ovarian serous cystadenocarcinoma, uterine corpus endometrial carcinoma and uterine carcinosarcoma, compared with corresponding healthy tissues in pancancer, indicating roles for viral invasion in most cancer types. Moreover, low NRP1 expression was significantly associated with long overall survival (OS) time in adrenocortical carcinoma, brain lower grade glioma, stomach adenocarcinoma and uveal melanoma, but with short OS time in KIRC only. The ENST00000374867.6 (NRP1-202) isoform is most highly expressed in most cancer types and thus could be involved in tumorigenesis and SARS-CoV-2 invasion in cancer patients. NRP1 may be involved in SARS-CoV-2 invasion in patients with cancer, including those with lung cancer.

Long-term clinical outcomes and prognosis after definitive radiotherapy for patients with cervical esophageal squamous cell carcinoma: a single-institution retrospective study.

Definitive radiotherapy has become a more common treatment for cervical esophageal squamous cell carcinoma (CESCC), but data about long-term clinical outcomes is still relatively sparse. The purpose of this study was to describe long-term clinical outcomes after definitive radiotherapy for CESCC, and identify the prognostic factors influencing these outcomes. We retrospectively analyzed all patients who received definitive radiotherapy for CESCC at our institution between 2006 and 2014. The overall survival (OS) rate, locoregional failure-free survival (LRFFS) rate, and toxicities were retrospectively evaluated during long-term follow-up. Univariate and multivariate analyses were performed to identify prognostic factors. A total of 120 patients were included for analysis. The median prescribed radiation dose for the gross tumor and metastatic lymph nodes was 60 Gy. Elective nodal irradiation (ENI) was performed on 99 patients (83%); 90 patients (75%) received concurrent chemotherapy. The OS rates were 22.7% at 5 years and 14.9% at 8 years. The LRFFS rates at 3, 5, and 8 years were 27.5%, 21.7%, and 15.0%, respectively. The univariate analysis suggested that N classification and non-regional lymph node metastasis (M1Lym) status were independent risk factors for overall survival (P<0.01). A dose of more than 60 Gy didn't have a statistically significant influence in the multivariate analysis, although a total dose of more than 60 Gy was associated with improved survival in the univariate analysis. Concurrent chemotherapy was not associated with OS or LRFFS time in the univariate or multivariate analysis. A total of 74 patients (61.7%) experienced locoregional treatment failure. The most commonly documented acute toxicities were grade 1 and grade 2 toxicities in 61 patients (50.8%). There were 2 patients diagnosed with hypothyroidism as a late toxicity event. Definitive radiotherapy is a reasonable curative treatment option with laryngopharyngeal preservation for CESCC patients. Radical treatments for lymph node metastases may improve the OS and LRFFS times. Monitoring for thyroid function may be warranted during long-term follow-up.

The prognostic role of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and systemic immune-inflammation index on short- and long-term outcome following surgery for spinal metastases.

Inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) have shown promise in predicting mortality in various types of cancer. The purpose of this study was to assess NLR, PLR, and SII in predicting 30-day mortality and overall survival (OS) among surgically treated patients with spinal metastasis. This was a retrospective study including 153 patients who underwent surgery for spinal metastasis between 2012 and 2022. Electronic medical records were manually reviewed, and NLR, PLR, and SII were calculated from preoperative neutrophil, platelet, and lymphocyte counts. Receiver operating characteristic curves with areas under the curve were generated to determine cutoff values. Logistic regression was used to determine the odds ratios (ORs) for 30-day mortality. The Kaplan-Meier method and Cox regression were used to determine the hazard ratio (HR) for OS limited to 5 years postoperatively. Preoperative cutoff values were as follows: NLR > 10.2, PLR > 260, and SII > 2900. Overall, 35.9% (55/153) of patients had elevated NLR, 45.7% (70/153) had elevated PLR, and 30.7% (47/153) had elevated SII. The overall 30-day mortality was 8.5% (13/153). After controlling for confounders such as performance status and primary tumor type, high NLR (OR 5.20, 95% CI 1.21-22.28; p = 0.026) and SII (OR 4.92, 95% CI 1.17-20.63; p = 0.029) were associated with increased odds of 30-day postoperative mortality. The median OS time in the study population was 26 months (95% CI 12-40 months). After controlling for confounders such as Eastern Cooperative Oncology Group status, primary tumor, and hypoalbuminemia, high NLR was associated with shorter OS (HR 2.23, 95% CI 1.48-3.97; p = 0.003). High preoperative NLR and SII were independently associated with 30-day postoperative mortality in this study. Elevated NLR was also found to be associated with shorter OS. The prognostic role of these metrics warrants further investigation.

Allogeneic Stem Cell Transplantation in Adolescent and Adult Patients with Acute T Cell Lymphoblastic Leukemia / Lymphoma : Single Center Experience of 143 Patients

Background: T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/-LL) is an aggressive hematological neoplasm originates from T-cell progenitors. T-ALL and T-LL are distinguished by the presence of more or &amp;lt;20% marrow blasts, respectively. Allogeneic hematopoietic cell transplantation (SCT) is typically recommended for adults with T-ALL in second or later complete remission (CR2+), but also may be offered to patients in first CR (CR1) with high-risk features. Our center reported previously outcomes of allogeneic HCT (allo-SCT) in 53 adolescent and young adults of T-ALL ( Biol Blood Marrow Transplant. 2012;18(12):1897-1904). Patients and Methods: We analyzed the outcomes of adults (age &amp;gt;14years) with T-ALL who received allo-SCT at King Faisal Specialist Hospital and Research Center between January 1985 and September 2018. Patients eligible for allo-SCT included HR patients in CR1 and any patient in &amp;gt; CR2 or relapse. Patients in CR1 had one or more of the following HR features: WBC count at presentation &amp;gt; 100,000/mm3, residual disease in bone marrow (BM) at day 14 postinduction, central nervous system (CNS) involvement at diagnosis and the need for more than one induction regimen to achieve CR1. Full-intensity conditioning regimens were used for all patients. The majority of patients (95.1%) received cyclophosphamide 60 mg/kg once daily i.v. for 2 consecutive days (total dose, 120 mg/kg), followed by 12 Gy of fractionated total body irradiation (TBI) given in 6 fractions. Seven patients (4.9%) received busulfan 16 mg/kg (1 mg/kg per dose orally every 6 hours over 4 consecutive days) and cyclophosphamide 60 mg/kg once daily i.v. for 2 consecutive days (total dose, 120 mg/kg).Short-course methotrexate plus cyclosporine (MTX/CSA) was the GVHD prophylaxis regimen used, in all patients. Results: 143 patients underwent allo-SCT and were included in this study; some of them were referred in CR for allo- SCT after undergoing induction chemotherapy outside our institution. Median age was 20 years (range, 14-52).Majority of patients were males 116 (80.6%). Extramedullary presentation was reported in 34 patients (23.8 %) with CNS involvement in 15 patients (10.5%). For SCT outcomes, the incidence rates for relapse 27.1%, acute GVHD 45.8%, grade II-IV acute GVHD was 29.9% and that of chronic GVHD was 38.9%, extensive chronic GVHD was 21.5%. GVHD relapse free survival (GRFS) was reported in 27.1%. The majority of relapses occurred within 1 year after SCT. The cumulative incidence of relapse (CIR) at 1 year was 22.4% 95% CI (15.9 - 29.5), at 2 years was 23.8.8% 95% CI (17.2 - 31) and at 5 years was 25.9% 95% CI (19 - 33.3). Other outcomes, Hemorrhagic cystitis (HC) was noted in 9.7%, sinusoidal obstruction syndrome (SOS) 9% The mean time for overall survival (OS) was 166.77 months (95% CI = 136.54 - 197), and the median survival time was 41 months (95% CI = 15 - 266). For the CR1 group was 205.63 months (95% CI = 166.59 - 244.66). At 10 years, OS of the CR1 group was 74.44 months (95% CI = 63.67 - 85.22), and for the &amp;gt; CR2 group was 35.36 months (95% CI = 24.39 - 46.32); p= 0.0001 PFS analysis showed, the overall mean survival time for disease progression at 5 years was 33.16 months (95% CI = 28.77 - 37.54), and the median survival time was 32 months (95% CI = 12 - 55). For the CR1 group was 39.82 months (95% CI = 34.54 - 45.09), and for the &amp;gt;CR2 group was 22.83 months (95% CI = 16.02 - 29.64), p &amp;lt; 0.0001. At 10 years, PFS for the CR1 group was 74.95 months (95% CI = 63.58 - 86.31), and for the &amp;gt;CR2 group was 41.24 months (95% CI = 27.37 - 55.11) with statistically significantly difference, p &amp;lt; 0.0001. On multivariate analysis, chronic GVHD was significantly associated with a lower OS (P=0.006) and PFS (P=0.01).Disease status at SCT remained significantly associated with PFS (P=0.02),but not OS (P=0.07). The presence of extramedullary disease and CNS involvement at diagnosis had no effect on the different outcomes. Conclusions: Allo-SCT could provide better disease control for HR patients with T-ALL/LL in CR1. Dismal outcomes are reported in patients beyond CR1 with early relapses post allo-SCT are almost inevitable. Better understanding of disease's molecular background in addition to MRD applications, could help to identify more patients in CR1 status who might benefit from allo-SCT. Post SCT strategies including maintenance or pre-emptive interventions might be needed to improve SCT outcomes for T-ALL

Cardiotoxicity Related Mortality Among Children with Acute Myeloid Leukemia in Low Middle Income Countries: Is It Treatment or Sepsis Related?

Background: Heart disease and cancer are two major causes of morbidity and mortality worldwide, accounting for at least 70% of the medical reasons for mortality across the globe. Modern treatment strategies led to improvements in cancer survival, however, these gains might be offset by the potential negative effect of cancer therapy on cardiovascular health. Over the last few decades, cooperative oncology group trials for pediatric acute myeloid leukemia (AML) have improved overall survival (OS) to nearly 65% by combining intensive chemotherapy with improved supportive care. Despite their efficacy, anthracyclines are linked to an increased risk of cardiotoxicity. Objectives:The study aimed to describe the incidence of cardiotoxicity among pediatric patients with acute myeloid leukemia, assess the effect of cardiotoxicity on treatment outcome in terms of overall survival (OS) and event free survival (EFS) and to determine the different risk factors (Age, gender, body mass index, cumulative doses of anthracyclines and sepsis) that may contribute to cardiotoxicity. Patient and Methods: A retrospective study, conducted at the National Cancer Institute (NCI), Cairo University, Egypt.,that included all pediatric patients ≤ 18 years old diagnosed and treated as Acute Myeloid Leukemia (AML) during the period from the first of January 2015 to the end of December 2019. Retrospective analysis of the different features of cardiotoxicity associated with the treatment of AML. Results : The study included 142 patients with a median age of 8.5 years old and M/F ratio 1.2:1.Out of the total study population, Eighty four patients (59.2%) developed cardiotoixicity in which 59.5% were acute onset cardiotoxicity and 40.5 % were chronic early cardiotoxicity and there was no detected cases of chronic late cardiotoxicity.Cardiac dysfunction was detected in 65/142 (45.8%) patients at time of death in association with sepsis. The cumulative incidence of cardiotoxicity was higher in the presence of blood stream infection with p value (p&amp;lt;0.001).55/84 (65.5%) patients with cardiotoxicity showed progressive cardiac dysfunction and they all died due to sepsis that was associated with cardiac dysfunction. At the end of the study the OS and EFS were 16.2 % and the median survival time was 1.9 month.The cumulative OS,EFS and the median survival time were reduced in the presence of acute cardiotoxicity with statistical significant p-value (p&amp;lt;0.001). Conclusion: The incidence of cardiotoxicity is high among pediatric AML patients and the most important risk factor for cardiotoxcity is blood stream infection. The Cumulative OS, EFS and median survival time are reduced in patients with acute cardiotoxicity which represents a major challenge that warrants more attention to the field of cardio-oncology.

Outcomes of Incorporating IV Daratumumab for the Treatment of AL Amyloidosis in Real World Patients from a Multicenter Registry in Latin America

Introduction: AL amyloidosis is characterized by the extracellular deposition of immunoglobulin light chains. Daratumumab is an anti-CD38 monoclonal antibody that has demonstrated outstanding results in the treatment of AL amyloidosis, achieving rapid and deep responses and improving OS. Nevertheless, patients with advanced cardiac disease have been usually excluded from clinical trials and data from real world patients in Latin America is lacking. Moreover, subcutaneous Daratumumab is not available in most countries in the region. Objective: To describe hematological (HR) and organ response, overall survival (OS) and event-free survival (EFS) of incorporating IV Daratumumab for the treatment of AL amyloidosis in real world patients from 5 centers in Argentina Materials and methods: Multicenter, retrospective cohort study of patients older than 18 years with a histopathological diagnosis of AL Amyloidosis and treated with at least one cycle in first-line (Group 1) or subsequent lines of treatment (Group 2) with Daratumumab IV, included in the registry of amyloidosis (RIA, NCT01347047). Data were collected from medical records in an standardized electronic clinical report form (RIA Redcap). The registry includes data for baseline demographics, medical history, comorbidities, physical examinations, laboratory, and imaging exams. Treatments were prescribed by the physician, according to the hospital's protocol. All patients were followed from first daratumumab infusion till death or lost to follow up for HR (as per response criteria by the International Amyloidosis Society, complete response [CR], very good partial response [VGPR], partial response [PR], no response [NR]), OS (time from diagnosis to death), progression free survival (PFS: time from diagnosis to disease progression or death). Adverse events were reported based on CTCAE. Overall and progression-free survival was estimated using Kaplan Meier. Results Thirty-seven patients with AL amyloidosis were included in the study. The characteristics of the population are summarized in Table 1. Twenty-four patients (65%) had cardiac involvement, 25 (68%) renal involvement, and 14 (40% ) both. Of the patients with cardiac involvement, 20 had cardiac stages Mayo 2012 III/IV. Group 1 included 18 patients who received daratumumab (48%), 17 in combination with CyborD. Group 2 included 19 patients (51%), 12 received Daratumumab in combination with dexamethasone, 5 with CyborD and 2 with lenalidomide. Thirty-three patients (90%) achieved HR, the median time to best hematologic response was 2 months (IQR 1-9 months). Seventeen patients (59%) achieved CR (group1 n=8 Group2 n=9), 9 MBRP (group1 n=4 group2 n=5), 7 PR (group1 n= 5 group2 n=2). Of the 20 patients with Mayo stages III/IV, 18 achieved hematologic response and 9 cardiac response. Three patients had stable disease, all of them were relapsed.. Three patients presented subsequent relapses. The Organ response rate was 59% (n=22, IC 45-75), 14 renal response, median time to response 8 months (IQ R4,6-14,1), 13 cardiac response, median time to response 6,4 months (IQR 6,4-6,4). Five patients had response of both organs. The median follow-up of the entire cohort was 18 months (CI 11-75). The median EFS at 1 year was 88% (CI 71-95) and at 2 years 83% (CI 64-93). Median OS at 12 months was 91% (CI 75-97) and at 24 months 86% (CI 68-95). There were 7 deaths in the entire cohort, 5 were due to cardiac complications associated with amyloidosis. Five of the deceased patients had achieved a HR. Eleven patients presented adverse events, mainly infectious complications, 5 of them grade 3 or 4. Conclusions: This study provides real-world evidence for Daratumumab IV treatment in patients with AL amyloidosis in the first line and at relapse, achieving fast and profound HR, which translated into a high organ response rate and improvement in OS and PFS. In our cohort, most patients achieved HR with a median time to best response at 2 months consistent with what is reported in the bibliography. This study is relevant since it is a real life study, in which intravenous daratumumab was used since the subcutaneous formulation is not available in most Latin American countries and also included patients with advanced stages achieving responses in this high risk subgroup. Treatment with Daratumumab should be considered a therapy of choice in AL amyloidosis, even in patients with advanced cardiac stages.

Correlation between Real-World Progression-Free Survival (rwPFS) and Overall Survival (OS) in Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) Who Relapsed or Are Refractory, Intolerant, Resistant to Treatment with a Bruton's Tyrosine Kinase Inhibitor (BTKi)

Introduction: Given the long maturation time of OS, PFS is often used in oncology and hematology as a surrogate for OS. However, the association between the two endpoints varies across cancer types. In CLL clinical trial populations, PFS and OS were shown to be strongly correlated in patients receiving at least two lines of therapy (LOT). The present study used real-world individual patient data to evaluate the strength of correlation between real-world PFS (rwPFS) and OS in CLL/SLL patients who relapsed or were resistant/refractory/intolerant to treatment with a covalent BTKi. Methods: A retrospective chart review was conducted of adult CLL/SLL patients at Dana-Farber Cancer Institute who were treated with at least one covalent BTKi and relapsed or were resistant/refractory/intolerant to the treatment and have discontinued BTKi. Patients were included if they had records available from 6 months before to 12 months after initiation of the first observed (index) BTKi, and were excluded if they were treated with a non-hormonal antineoplastic agent for other primary malignancies in the period between CLL/SLL diagnosis and receipt of their first BTKi. Demographic and clinical variables, oncologic and medical histories, treatments, and clinical outcomes were abstracted from patients' medical charts. Time to event endpoints were described using Kaplan-Meier curves. Time to progression (TTP) was defined as time from index to progression. OS was defined as time from index to death; patients were censored at the last visit if they did not die. rwPFS was defined as the time to progression or death; patients who did not progress or die were censored at index BTKi treatment discontinuation. Fleischer's method was used to estimate the individual-level Pearson correlation coefficient between rwPFS and OS among patients treated with BTKi in any line of treatment. Confidence intervals (CIs) were calculated by bootstrapping (1000 replicates). Results: A total of 104 patients who initiated treatment with the index BTKi from 07/2011 to 09/2019 and relapsed or were resistant/refractory/intolerant to the treatment were included in the analysis. Median (interquartile range [IQR]) age at BTKi initiation was 66.7 (60.3-73.0) years, median (IQR) time from index BTKi initiation to last clinical visit or death was 5.7 (3.3-7.0) years. Among patients with a known index BTKi LOT (N=102 [98%]), 28% received the index BTKi in first line, 32% in second line, 23% in third line, 12% in fourth line, and 6% in or after the fifth line. An assessment date for response to the index BTKi and for whether a patient had progressed was available for 95 patients (91%) ( Table 1). Among these patients, progression after index BTKi treatment was observed for 48 (51%) patients. Median (95% CI) time from BTKi initiation to progression was 3.7 (2.6, 4.1) years. More than one-third of patients (35%) died and median (95% CI) OS was 8.9 (6.7, not reached) years. 7 patients died without progressing and cause of death was available for 5 of these patients: 3 died because of an infection, 1 because of a secondary malignancy, and 1 because of other unspecified causes. 58% patients progressed or died and median (95% CI) rwPFS was 3.2 (2.6, 3.9) years. The correlation (95% CI) between rwPFS and OS was 0.79 (0.63, 0.94). Conclusions: This analysis found a strong, positive, and significant correlation between rwPFS and OS in patients with CLL/SLL who received treatment with a covalent BTKi and relapsed on or were resistant/refractory/intolerant to the treatment. These findings reinforce the hypothesis that rwPFS may be a useful early endpoint for evaluating the effectiveness of BTKi treatment outside of clinical trials among the patient population of CLL/SLL patients who relapsed or were refractory/resistant/intolerant to BTKi, at time points when OS is not mature. However, further analysis of the change in rwPFS that predicts an improvement in OS (surrogate threshold effect) is required to establish rwPFS as a valid surrogate for OS.

Anti-PD-1 Antibody Sintilimab in Combination with Anlotinib and Pegaspargase As a Highly Effective Salvage Regimen for the Treatment of Relapsed or Refractory Natural Killer /T-Cell Lymphoma

Natural killer/T-cell lymphoma (NKTCL) is a rare and aggressive neoplasm associated with Epstein-Barr virus (EBV) infection. When patients experience relapse or disease progression after initial treatment, options for salvage therapy are limited. Targeting the PD-1/PD-L1 pathway has emerged as a highly potent treatment approach for NKTCL. However, the overall response rate (ORR) and complete response (CR) rate were limited with a short median progression-free survival (PFS) of 2.7 months. Therefore, improving the efficacy of immune checkpoint inhibitors is a critical clinical concern. In this study, we reported the efficacy and safety of a novel triplet regimen called LEAP, which combines PD-1 blockade (sintilimab 200mg on day 1), pegaspargase (2500U/m2 capped at 3750U on day 1), and angiogenesis inhibitor anlotinib (8mg on day 1-14), as a salvage treatment for relapsed/refractory (R/R) NKTCL. From March 2019 to May 2020, a total of 33 patients with R/R NKTCL were included in this study. The median age of patients was 48 years (range: 18-76), with 75.8% being male. At study entry, 88% of patients had stage IV disease, while 4 patients had stage II disease, with a history of primary refractory response to radiotherapy and L-asparaginase-based combination therapy. Moreover, 69.7% of patients had refractory disease, including those who were progressive or non-responsive to L-asparaginase-based regimens. Additionally, 10 patients experienced relapse or disease progression within 6 months after prior L-asparaginase-based therapy, and 10 patients had a history of PD-1/PD-L1 blockade monotherapy. A total of 221 cycles of the LEAP regimen were administered to these patients. The median number of cycles was 8 (range: 2-8). All patients reported at least one or more adverse events (AE). Hematological toxicities were mild, with no grade 3/4 neutropenia, anemia, or thrombocytopenia observed. Non-hematological AEs were common, and the most frequent (&amp;gt;20%) included hypofibrinogenemia (66.7%), hyperbilirubinemia (57.5%), APTT prolongation (54.5%), ALT elevation (54.5%), AST elevation (51.5%), hypoalbuminemia (48.5%), appetite loss (60.6%), nausea (57.5%), fatigue (57.5%), weight loss (42.4%), and edema (27.3%). These adverse events were typically attributed to pegaspargase. Other adverse events such as hyponatremia (24.2%), hypertriglyceridemia (21.2%), hyperglycemia (21.2%), hypothyroidism (30.3%), hypertension (24.2%), fever (39.4%), and dysphonia (21.2%) were most likely due to sintilimab or anlotinib. Most adverse events were manageable with supportive care. Among the 33 patients, the ORR was 81.8%, and CR was 45.5. The progression-free survival (PFS) rate at 1-year was 54.6% (95% CI, 36.3% to 70.0%), and at 2 years, it was 44.2% (95% CI, 26.6% to 60.4%). The median PFS time was 21.7 months. The overall survival (OS) rate at 1-year was 66.7% (95% CI, 47.9% to 80.0%), and at 2 years, it was 51.5% (95% CI, 33.5% to 66.9%). The median OS time was not reached during the study period. In conclusion, our study demonstrates that the LEAP regimen has a favorable safety profile, and is highly effective as a salvage treatment for patients with relapsed and refractory NKTCL.

Corelationship of Lymphocyte Subsets and Prognosis in Juvenile Myelomonocytic Leukemia

Objective: Juvenile Myelomonocytic Leukemia (JMML) is a rare hematopoietic stem cell malignant clonal disease in children and has the characteristics of MDS/MPN. Due to the poor response of JMML to chemotherapy, hematopoietic stem cell transplantation (HSCT) is currently the only cure method for JMML. Currently, there are some reports on the distribution of lymphocyte subsets in MDS. A significant lymphocytopenia was observed in MDS patients compared with similarly aged healthy people. Another study form Polish found patients with MDS have more CD3+T cells than healthy donors. But there are few related reports in JMML. The objective of this study is to analyze relationship between the distribution of lymphocyte subsets and prognosis in JMML patients, and explore new risk stratification indicatorsfor JMML personalized therapy. Method: This study retrospectively collected JMML patients clinical data from Institute of Hematology &amp; Blood Diseases Hospital of CAMS during Jan 2008 and Nov 2022. All completed complete blood count and peripheral blood classification, fetal hemoglobin (HbF), granulocyte colony-stimulating factor (GM-CSF) high sensitivity, bone marrow morphology, immune typing, molecular biology, cytogenetics and other tests. We analyzed the relationship between distribution of lymphocyte and prognosis in these patients. Result: 96 newly diagnosed JMML patients were admitted to this study. The median age at diagnosis was 25 (2-82) months, and male to female was 3.8:1. 66 cases underwent lymphocyte subsets by flow cytometry. Median percentage of lymphocytes is 34.3%(1.8%-90.4%, normal range: 20%-40%), median percentage of CD3+T cells is 54.85%(10.3%-91%, normal range: 57%-88%), median percentage of CD3+CD4+ T cells is 30.95%(3.54%-53%, normal range: 27%-58%), median percentage of CD3+CD8+ T cells is 18.4%(2%-49.1%, normal range: 16%-45%), median percentage of NK cells is 13.95%(2.3%-50.3%, normal range: 3%-32%), and median percentage of B cells is 23.25%(4%-69.6%, normal range: 4%-18%). These cases were followed-up to Jan 2023, with a median follow-up time of 12 months (1-104 months). The overall survival (OS) rate was 52.67%, with a median OS time of 12 months (0-103 months). There were significant differences in the percentage of CD3+T cells (30.89% ± 9.46% vs 59.05% ± 10%, P&amp;lt;0.01) and CD3+CD4+T cells (14.87% ± 5.82% vs 35% ± 5.41%, P&amp;lt;0.01) between children with single NRAS mutation and compound mutations (≥2 classical five Ras pathway mutation ). In PTPN11 mutation patients, there is a significant positive correlation between OS and the percentage of lymphocytes (P=0.018). Conclusion: Our study shows differences in percentage of CD3+ T cells and CD3+CD4+ T cells between patients with NRAS mutation and compound mutations. Patients with PTPN11 mutation and higher percentage of lymphocytes will have better prognosis.

The effects of dexmedetomidine on postoperative tumor recurrence and patient survival after breast cancer surgery: a feasibility study

PurposeDexmedetomidine (Dexmed) is a highly selective alpha 2 adrenoceptor (α2-AR) agonist with excellent sedation and analgesic effects and is frequently used in breast cancer surgery. However, the exact impact of Dexmed on breast cancer prognosis is still unclear. The primary objective of this pilot study was to explore study feasibility (recruitment and dropout rates) for future large-scale randomized controlled trial (RCT) to test the hypothesis that intraoperative Dexmed reduced recurrence-free survival (RFS) and overall survival (OS) in patients after breast cancer surgery.MethodsInterviews with patients were performed during the anesthetic preoperative visit for informed consent. Adult females scheduled for a mastectomy due to primary breast cancer were 1:1 randomised to saline (Group Control) or Dexmed (Group Dexmed) treatment groups. The primary outcomes were descriptions of study feasibility (recruitment and dropout rates). We also performed a preliminary analysis of RFS (time from surgery to the earliest date of recurrence/metastasis) and OS (time from surgery to the date of all-cause death) and collected data on percentages/numbers of circulating immune cells at pre- and 24 h post-operation.ResultsA total of 964 patients were screened; 40% (385/964) met the inclusion criteria, among which 39% (150/385) were enrolled and randomly assigned to either Group Control (n = 75) or Group Dexmed (n = 75). The median follow-up duration was 49 months (interquartile range (IQR): 34–58 months) for Group Control and 48 months (IQR: 33–60 months) for Group Dexmed. Five percent (5%, 8/150) patients were lost to follow-up and 1% (2/150) died. There was no significant difference in RFS and OS. The percentage/number of natural killer (NK), B and T-cell subsets and the CD4+/CD8+ ratio were similar between groups at 24 h post-operation.ConclusionThe pilot study was feasible to deliver. In a future definitive trial, the lower recruitment rate may be improved by increasing the number of anesthesiologists involved in the study. The study about the effects of Dexmed on long-term prognoses of breast cancer patients that is planned to follow this pilot study is a large-scaled randomized control study with the aim of providing evidence-based guidelines for rational use of Dexmed in patients undergoing breast cancer surgery.Trial registrationRegistered at ClinicalTrials.gov on October 20, 2016 (ID: NCT03109990).Graphical

TMIC-85. TGFB2 AND IFNGR2 MRNA EXPRESSION LEVELS IN THE TUMOR MICROENVIRONMENT (TME) PROGNOSITICALLY IMPACT OS IN PEDIATRIC DIPG PATIENTS

Abstract DIPG patients expressed significantly higher levels of TGFB2 and IFNGR2 than control pons samples and the expression profile indicated higher levels of TGFB2 than TGFB1 and TGFB3 in DIPG patients suggesting TGFB2 mRNA level is preferentially increased in DIPG patients. TGFB2 is a prognostic indicator (HR for patients in the TGFB2high group of DIPG patients = 2.88 (1.12-7.39); P = 0.028) for poor overall survival (OS) independent of IFNGR2 levels, the age of the patient, and the significant interaction effect observed between IFNGR2 and TGFB2. Predictive modeling using the Cox regression parameters showed that the context of low expression of IFNGR2, TGFB2low resulted in more favorable OS times compared to TGFB2high whereby the median OS time of 11 months for the TGFB2low group of patients was greater than the upper 95% confidence limit for the TGFB2high group of patients (Median = 7 months; Upper 95% Confidence interval = 10 months). At higher levels of IFNGR2 expression, the TGFB2high group of patients exhibited a median OS time of 15 months that was within the (95% confidence interval for the TGFB2low group of patients (Median = 13 months; 95% CI = 10-17 months). Worse survival outcomes comparing DIPG patients with high versus low TGFB2 levels in the context of low levels of IFNGR2 levels suggest that abrogating the TGFB2 mRNA expression in the immunologically cold tumor microenvironment indicated by low levels of IFNGR2 expression can potentially treat pediatric DIPG patients. Furthermore, DIPG patients with low levels of JAK1 or STAT1 mRNA expression in combination with TGFB2high also exhibited poor OS outcomes suggesting that the inclusion of (Interferon-gamma) IFNγ to stimulate and activate JAK1 and STAT1 in anti-tumor immune cells present the brainstem tumor microenvironment can enhance the effect of TGFB2 blockade.