Median Survival Of Patients Research Articles

Long-term follow-up of humanized and murine CD19 CAR-T-cell therapy for B-cell acute lymphoblastic leukemia

Objective: Murine CD19 chimeric antigen receptor T-cell (CAR-T) products have been approved for the treatment of refractory/relapsed (R/R) B-cell acute lymphocytic leukemia (B-ALL) ; moreover, humanized products are also undergoing clinical trials. This study aimed to explore the differences in safety and short- and long-term follow-up efficacy between humanized and murine CD19 CAR-T-cells for treating relapsed and refractory B-ALL. Methods: Clinical data of 80 patients with R/R B-ALL treated with CD19-targeted CAR-T-cells at the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology between May 2016 and March 2023 were analyzed, which included 31 patients with murine CAR-T and 49 with humanized products. Results: The proportion of patients with cytokine-release syndrome (CRS) in the murine and humanized groups was 63.1% and 65.3%, respectively. Moreover, a higher proportion of patients suffered from severe CRS in the murine group than in the humanized CAR-T group (19.4% vs 8.2%, P=0.174). Furthermore, one patient per group died of grade 5 CRS. The incidence of grade 1-2 immune effector cell-associated neurotoxicity syndrome (ICANS) was 12.9% and 6.1%, respectively; severe ICANS were not observed. Among patients receiving murine CAR-T-cells, an overall response (OR) was observed in 74.2%. Conversely, the OR rate of patients receiving humanized CAR-T-cells was 87.8%. During the median follow-up time of 10.5 months, the median recurrence-free survival (RFS) of patients with murine CAR-T-cells was 12 months, which was as long as that of patients with humanized CAR-T-cells. The median overall survival (OS) were not reached in both groups. Of the 45 patients with a bone marrow burden over 20% at baseline, humanized CAR-T therapy was associated with a significantly improved RFS (43.25% vs 33.33%, P=0.027). Bridging transplantation was an independent factor in prolonging OS (χ(2)=8.017, P=0.005) and PFS (χ(2)=6.584, P=0.010). Common risk factors, such as age, high proportion of bone marrow blasts, and BCR-ABL fusion gene expression, had no significant effect on patients' long-term follow-up outcomes. Three patients reached complete remission after reinfusion of humanized CAR-T-cells. However, one patient relapsed one month after his second infusion of murine CAR-T-cells. Conclusions: The results indicate that humanized CAR-T therapy showed durable efficacy in patients with a higher tumor burden in the bone marrow without any influence on safety. Moreover, it could overcome immunogenicity-induced CAR-T resistance, providing treatment options for patients who were not treated successfully with CAR-T therapies.

Antiphospholipid syndrome in rural, remote, and First Nations peoples in the Top End of the Northern Territory, Australia

BackgroundThe Northern Territory of Australia has a high proportion of First Nations peoples living in remote communities and a high burden of chronic autoimmune diseases. The epidemiology and clinical outcomes of antiphospholipid syndrome (APS) in First Nations Australians are poorly characterized. ObjectivesTo determine the epidemiology, presenting features, and outcomes of patients with APS using an 18-year retrospective cohort of newly diagnosed patients presenting to Royal Darwin Hospital (2002-2020). MethodsPatients admitted to Royal Darwin Hospital with a new incident diagnosis of APS between January 2002 and December 2020 were identified and followed until December 2022, with data on baseline demographics, clinical and laboratory features, and overall survival extracted from electronic and paper medical records. ResultsFifty-three patients with APS were included, of whom 40 (75%) were First Nations and 46 (87%) were female. Thirty (75%) of First Nations patients with APS resided in very remote Australia vs 0 (0%) non–First Nations patients. Eighteen cases (34%) had primary APS, and 35 cases (66%) had secondary APS, most in association with lupus. Eight (15%) cases developed catastrophic APS (CAPS), all in First Nations patients. There were 13 deaths (of which 11 were among First Nations patients). Patients with CAPS had significantly shorter median overall survival (8.3 years from diagnosis), with median survival in non-CAPS patients not reached (P = .003). ConclusionThere is a high prevalence of APS in First Nations patients living in very remote Australia admitted for tertiary care in the tropical north of the Northern Territory, Australia. The rate of CAPS in First Nations patients was high, and CAPS was associated with significantly shorter survival. Larger prospective studies are required to inform improved models of care for First Nations and remote Australians living with APS.

THU541 Impact Of Gender On Treatment Decisions And Outcome In Patients With Neuroendocrine Neoplasms

Abstract Disclosure: J. Beck: None. A. Siebenhüner: None. D. Wild: None. E.R. Christ: None. J. Refardt: None. Introduction/Background: Gender differences affect the treatment of several diseases in both male and female patients. However, the influence of gender on treatment decisions and outcome in neuroendocrine neoplasms (NENs) has scarcely been investigated. Aims: Comparison of tumor characteristics, treatment decisions and outcome of patients with NENs, stratified by gender. Material and Methods: Retrospective analysis of the SwissNET cohort involving NENs of gastroenteropancreatic, pulmonal or unknown origin from 07/14 – 09/21. Site of origin, tumor grading, time to first treatment, choice of treatment and overall survival was assessed. Results: 2329 patients were included in the analysis with 54% being male and 46% female patients. No significant difference in site of origin, tumor grading and staging was found between male and female patients. There was also no difference in time of symptoms onset until diagnosis and first treatment intervention. Surgery was performed in 66.3% of male and 71% of the female patients, p=0.016. Meanwhile, male patients received more often PRRT (22% vs 19.3%, p=0.007) and chemotherapy (15.9% vs 12.7%, p=0.032). Despite the similar tumor characteristics, the median overall survival of male patients was significantly lower compared to female patients (Male: 124.8 months, Female: 158.5 months, p<0.001). Interestingly, this difference was most pronounced in patients with lung NENs (Male: 142 months, Female: not reached) and cancer of unknown origin (Male: 18.5 months, Female: 35 months). Conclusions: Male gender seems to be a risk factor for worse outcome, specifically for lung NENs and NENs of unknown origin. The underlying mechanisms of these findings remain to be established. Presentation: Thursday, June 15, 2023

Magnetic and Fluorescent Dual-Labeled Genetically Encoded Targeted Nanoparticles for Malignant Glioma Cell Tracking and Drug Delivery.

Human glioblastoma multiforme (GBM) is a primary malignant brain tumor, a radically incurable disease characterized by rapid growth resistance to classical therapies, with a median patient survival of about 15 months. For decades, a plethora of approaches have been developed to make GBM therapy more precise and improve the diagnosis of this pathology. Targeted delivery mediated by the use of various molecules (monoclonal antibodies, ligands to overexpressed tumor receptors) is one of the promising methods to achieve this goal. Here we present a novel genetically encoded nanoscale dual-labeled system based on Quasibacillus thermotolerans (Qt) encapsulins exploiting biologically inspired designs with iron-containing nanoparticles as a cargo, conjugated with human fluorescent labeled transferrin (Tf) acting as a vector. It is known that the expression of transferrin receptors (TfR) in glioma cells is significantly higher compared to non-tumor cells, which enables the targeting of the resulting nanocarrier. The selectivity of binding of the obtained nanosystem to glioma cells was studied by qualitative and quantitative assessment of the accumulation of intracellular iron, as well as by magnetic particle quantification method and laser scanning confocal microscopy. Used approaches unambiguously demonstrated that transferrin-conjugated encapsulins were captured by glioma cells much more efficiently than by benign cells. The resulting bioinspired nanoplatform can be supplemented with a chemotherapeutic drug or genotherapeutic agent and used for targeted delivery of a therapeutic agent to malignant glioma cells. Additionally, the observed cell-assisted biosynthesis of magnetic nanoparticles could be an attractive way to achieve a narrow size distribution of particles for various applications.

Racial Disparities in the Utilization of Stereotactic Body Radiation Therapy (SBRT) in Patients with Hepatocellular Carcinoma

SBRT has now been demonstrated to improve OS, PFS and TTP in patient with hepatocellular carcinoma (HCC) when compared to systemic therapy alone. Disparities in the availability and utilization of SBRT for minority racial patients may affect oncologic outcomes. This study examines racial and sociodemographic disparities in the utilization of SBRT for HCC patients. In this registry-based cohort study, data from the American College of Surgeons National Cancer Database (NCDB) from 2004 - 2017 was analyzed. Adults with a new diagnosis of localized, non-metastatic, HCC were included in this analysis. Patients were sub-grouped by race and whether they were treated with liver SBRT. In this analysis, SBRT was defined as radiation delivered in 3-5 fractions and in the 30-60Gy range. The primary outcome of this study was the utilization rate of liver SBRT in HCC, depending on race. Survival was also examined in these patients. Statistical analysis was performed using SPSS v28 for univariate and multivariate logistical regression and Kaplan-Meier analysis. From 2004 - 2017, 95132 cases of localized HCC were identified in patients who were white, non-Spanish, non-Hispanic (WNH) and 40964 cases who were black or Hispanic/Spanish (BH). Of all these patients, only 1963 patients, or 1.4%, were treated with liver SBRT. Comparing WNH patients to BH patients, 1423 (1.5%) WNH patients were treated with SBRT and 334 (0.8%) BH patients were treated with SBRT (p<0.001). Looking at the number of patients treated with SBRT each year, there has been a yearly increase in the use of liver SBRT, from 48 patients in 2007 to 340 patients in 2017. The utilization of SBRT in WNH patients has increased at a higher rate than for BH patients over this time period. The median survival for patients with localized HCC was similar for both WNH and BH patients with a median survival of 17 months (p = 0.36). However, patients who were treated with liver SBRT had an improved median survival of 25 months for WNH patients and 34 months for BH patients (p<0.001). Overall, liver SBRT is severely underutilized for patients with localized HCC in the patient population represented in this database, and fewer BH patients are treated with liver SBRT compared with WNH patients. Liver SBRT is associated with improved survival of HCC patients in this study. With the findings of the RTOG 1112 trial, demonstrating improved OS and PFS with the use of SBRT for HCC, it is essential to adopt liver SBRT more broadly and to develop strategies to reduce the racial disparities in utilization.

External Validation of the Graded Prognostic Assessment for Patients with Non-Small Cell Lung Cancer and Brain Metastases Using Molecular Markers (Lung-molGPA)

Patients with non-small cell lung cancer (NSCLC) and brain metastases represent a markedly heterogeneous population. The original diagnosis-specific graded prognostic assessment is a prognostic index based on data from patients diagnosed between 1985 and 2005 and includes patients age, performance status, extracranial disease, and number of brain metastases. An updated prognostic index (Lung-molGPA) that incorporates molecular features (EGFR and ALK alterations) was created in 2016 based on the North American retrospective database analysis of 2186 patients with NSCLC and newly diagnosed brain metastases between 2006 and 2014. The aim of this study is to validate the Lung-molGPA model in an independent Asian patient population. Four hundred thirty-three patients (368 adenocarcinoma and 65 nonadenocarcinoma) with NSCLC with newly diagnosed brain metastasis between 2005 and 2017 were reviewed retrospectively and scored using the Lung-molGPA model. The overall median survival for the cohort in the present study was 14 months (16.5 months in the adenocarcinoma and 8.0 months in the nonadenocarcinoma, respectively; p = 0.003). For patients with adenocarcinoma, the median survival for patients with a Lung-molGPA score of 3.5 to 4.0 was 44.7 months, while the median survival was only 8.9 months in patients scoring 0-1.0, 17.0 months in patients scoring 1.5-2.0, and 30.2 months for scores of 2.5-3.0 (p <0.0001). For patients with nonadenocarcinoma, the median survival for scores 0-1.0, 1.5-2.0, and 2.5-3.0 were 6.7, 10.3, and 13.2 months, respectively (p = 0.038). Survival for patients with NSCLC and brain metastases varies widely. This study provides an independent validation of the 2016 Lung-molGPA in Asian patients.

Overall survival of patients with cHL who progress after autologous stem cell transplant: results in the novel agent era

AbstractIn the pre–novel agent era, the median postprogression overall survival (PPS) of patients with classic Hodgkin lymphoma (cHL) who progress after autologous stem cell transplant (ASCT) was 2 to 3 years. Recently, checkpoint inhibitors (CPI) and brentuximab vedotin (BV) have improved the depth and durability of response in this population. Here, we report the estimate of PPS in patients with relapsed cHL after ASCT in the era of CPI and BV. In this multicenter retrospective study of 15 participating institutions, adult patients with relapsed cHL after ASCT were included. Study objective was postprogression overall survival (PPS), defined as the time from posttransplant progression to death or last follow-up. Of 1158 patients who underwent ASCT, 367 had progressive disease. Median age was 34 years (range, 27-46) and 192 were male. Median PPS was 114.57 months (95% confidence interval [CI], 91-not achieved) or 9.5 years. In multivariate analysis, increasing age, progression within 6 months, and pre-ASCT positive positron emission tomography scan were associated with inferior PPS. When adjusted for these features, patients who received CPI, but not BV, as first treatment for post-ASCT progression had significantly higher PPS than the no CPI/no BV group (hazard ratio, 3.5; 95% CI, 1.6-7.8; P = .001). Receipt of allogeneic SCT (Allo-SCT) did not improve PPS. In the era of novel agents, progressive cHL after ASCT had long survival that compares favorably with previous reports. Patients who receive CPI as first treatment for progression had higher PPS. Receipt to Allo-SCT was not associated with PPS in this population.

BIOPSY VS BEST SUPPORTIVE CARE IN GLIOBLASTOMA: IMPACT OF NO POST-OP RADIOTHERAPY ON OVERALL SURVIVAL

Abstract AIMS Best supportive care (BSC) is a management option generally considered glioblastoma patients with poor performance status, multiple co-morbidities or extensive disease. Navigated biopsy is recommended if there are multi- focal or multicentric disease. Patients are considered for biopsy based on performance score and co-morbidities with the aim of delivering post-operative radiotherapy. However, some patients are not offered radiotherapy. We examined patients who underwent biopsy and BSC to determine their overall outcomes METHOD Data from the neuro-oncology database and electronic patient records between 01/01/2018- 31/12/2022 were analyzed using GraphPad. RESULTS A total of 112 glioblastoma patients were included, 73 (median age: 65 years) patients underwent biopsy with 39 for best supportive care (median age: 80 years). The median overall survival for biopsy patients was 22.1 weeks (0.6-258) compared to 7.9 weeks (0.7-65.4) for BSC. 38 underwent post-operative radiotherapy. We further looked at biopsy patients that did not receive post-operation radiotherapy, 35 were identified and compared to BSC patients. There was a significant difference observed in overall survival between BSC (7.9 weeks) and No radiotherapy (14.7 weeks) groups (p&amp;lt;0.05). CONCLUSIONS We hypothesize that difference in overall survival between BSC and No radiotherapy patients could be due to 79.5% of BSC patients having significant co-morbidities compared to only 57% No radiotherapy patients. The group of BSC patients were also slightly older compared to patients that underwent biopsy. An interesting finding is that about 46% of BSC patients were not prescribed any dexamethasone compared to 11% of biopsy patients.

P06.01.A HAS THE USE OF DUAL AGENT IMMUNOTHERAPY BEEN ALTERING THE INCIDENCE OF MELANOMA BRAIN METASTASES? A POPULATION-LEVEL ANALYSIS AND SINGLE-INSTITUTION VALIDATION

Abstract BACKGROUND Dual agent immunotherapy (dIT) has revolutionized the treatment of advanced melanoma, with recent clinical trials demonstrating its effectiveness in managing small, asymptomatic melanoma brain metastases (MBM) in the upfront setting. However, its potential role in preventing MBM has not been thoroughly investigated. MATERIAL AND METHODS A retrospective analysis was performed on the TriNetX database, which compiles clinical data from 92 healthcare organizations. Melanoma patients without MBM at diagnosis were divided into two groups: those who received ipilimumab alone (single immunotherapy, sIT) and those who received ipilimumab and nivolumab (dIT). The study compared the frequency of new asynchronous MBM diagnosis among the cohorts and analyzed the median overall survival (OS) of MBM patients using Kaplan Meier analysis and log-rank tests. Additionally, a retrospective cohort validation study was conducted on a sample of randomly selected patients treated at a single institution between 2012-2019. Electronic medical records were reviewed for demographics, melanoma treatment history, and clinical outcomes. RESULTS TriNetX identified a total of 732,555 melanoma patients, including 717,408 who did not receive immunotherapy (no-IT), 4,585 who received dual immunotherapy (dIT), and 4,101 who received single immunotherapy (sIT). The mean ages at melanoma brain metastases (MBM) diagnosis were 66.9, 61.5, and 63.2 years for each respective group. The prevalence of MBM was 1.5%, 9.6%, and 15.6% for no-IT, dIT, and sIT groups, respectively (p &amp;lt; 0.0001). DIT was associated with a lower rate of MBM compared to sIT(OR [95%CI], 0.64 [0.61-0.77]). After propensity score matching, the median overall survival for MBM patients was not statistically different between the no-IT, dIT, and sIT groups (347, 400, 414 days, respectively). In the validation group of 90 patients (30 no-IT, 27 sIT, 34 dIT), predominantly male (61.5%), stage III (62.5%), the prevalence of MBM was 13.8%, 59%, and 38.2% for each respective group for developing MBM (OR [95%CI], 2.35 [0.84-6.60], p=0.08). The mean time between immunotherapy initiation and MBM was 305 days for dIT and 500 days for sIT for patients who developed MBM. CONCLUSION The results suggest that using a combination of ipilimumab and nivolumab immunotherapy could be effective in reducing the incidence of brain metastases in advanced melanoma patients. Further investigation is needed to explore the potential preventive role of dIT in MBM development in this patient population.

Effect of blood type on mortality among patients with brain metastases

ObjectiveABO blood type has been associated with mortality among patients with cancer, but this association has thus far not been investigated among patients with brain metastases. Hence, we aimed to investigate the association between ABO blood type and mortality among patients who underwent surgical resection of brain metastases. MethodsA single-center retrospective study of patients who underwent surgical resection of brain metastases between 2011 and 2019 was conducted. Cox proportional hazards models were constructed, adjusting for potential confounders, to evaluate whether blood type was independently associated with overall mortality. ResultsA total of 158 patients were included in the analysis. The mean (SD) age of the cohort was 59.3 (12.0) years, and 67.7% of patients were female. The median overall survival of patients with blood type AB was 11.2 months, while the median overall survival of patients with blood types O, B, and A were 11.7, 13.5, and 14.4 months respectively. On univariate analysis, patients with blood type AB had a higher risk of overall mortality (p = 0.017). On multivariate analysis adjusting for potential confounders, blood type AB was again associated with a higher risk of overall mortality (HR: 2.29, 95% CI: 1.11–4.72, p = 0.025). ConclusionBlood type AB was independently associated with a higher risk of overall mortality among patients who underwent surgical resection of brain metastases, indicating the potential prognostic value of ABO blood type in brain metastases.

Early T-Cell Precursor Leukemia: A High-Risk Subtype of Acute Lymphoblastic Leukemia, Single Center Experience in Jordan

Background and ObjectivesEarly T-cell precursor (ETP) acute lymphoblastic leukemia/lymphoma (ALL/LBL) is a newly recognized entity of T-lymphoblastic leukemia/lymphoma. The optimal therapeutic approaches to adult patients are poorly studied. Patients and MethodsWe compared the outcomes of adult's patents with ETP-ALL/LBL who received frontline chemotherapy regimens with other T-ALL/LBL immunophenotypic subtypes. Patients with ETP-ALL/LBL were identified based on CD1a (-), CD8 (-), CD5 (-) (dim), and positivity for 1 or more stem cell or myeloid antigens. ResultsSixty-nine patients were included between the years 2010 and 2021 (19 ETP-T-ALL/LBL; 50 non ETP- T-cell ALL/LBL). The median age was 26 year (IQR: 21, 33). Fifty-six patients presented as ALL, while 16 with lymphoblastic lymphoma. Forty-seven patients achieved complete remission, and 43 were alive at last encounter. The complete remission rate in patients with ETP-ALL/LBL was lower than that of non-ETP-ALL/LBL patients (32% vs. 68%; P = .2), and the MRD at end of induction was significantly higher (26% vs. 6.2%, P < .001), and more likely to receive allo-SCT consolidation in CR1 (95% vs. 40%, P < .001). After a median follow-up of survivors of 48 months (range: 32-74 months), the median overall survival for patients with ETP-ALL/LBL was not reached versus 11.5 months for the non-ETP-ALL/LBL patients (P = .014)). Twenty-six patients receive allo-SCT in CR1. There was no significant difference in overall survival (79% vs. 70%; P = .49) between both transplant-cohorts in both groups. ConclusionETP-ALL/LBL represents a high-risk disease subtype of adult ALL. Novel treatment strategies are needed to improve treatment outcomes in this patient's population

Comparison of the effectiveness of chemotherapy combined with immunotherapy and chemotherapy alone in advanced biliary tract cancer and construction of the nomogram for survival prediction based on the inflammatory index and controlling nutritional status score.

To analyze the effectiveness of combining immune checkpoint inhibitors (ICIs) with first-line therapy in patients with advanced biliary tract cancer (BTC) and explore the biomarkers affecting the prognosis of immunotherapy, to construct a nomogram for the prediction of survival. A retrospective study was conducted to include a total of 209 patients with advanced BTC treated in the first line from 2018 to 2022, divided into a combination therapy group (n = 129) and a chemotherapy-only group (n = 80) according to whether ICIs were applied in combination. Univariate and multifactorial COX regression analyses were performed on variables that may affect prognosis to identify independent influences on patient prognosis, and this was used to create nomograms, which were then prospectively validated and calibrated. The median progression-free survival (mPFS) and median overall survival (mOS) of patients in the combination therapy group were higher than those in the chemotherapy alone group [hazard ratio (HR) = 1.152, 95% confidence interval (CI): 0.7848-1.692, p = 0.0004, and HR = 1.067, 95% CI: 0.7474-1.524, p = 0.0016]. The objective response rate (ORR) of patients in the combination therapy and chemotherapy alone groups was 39.5% (51/129) vs. 27.5% (22/80), and the disease control rate (DCR) between the two groups was 89.9% (116/129) vs. 83.8% (67/80). Univariate analysis revealed the gender, presence of long-term tobacco and alcohol, degree of histological differentiation, serum albumin level, presence of liver metastases, presence of multi-visceral metastases, response, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), glycoprotein antigen 19-9 (CA19-9), systemic inflammatory index (SII), and controlling nutritional status (CONUT) scores were statistically significant with patient prognosis (all P values < 0.05). Multi-factor COX regression analysis was continued for the above variables, and the results showed that NLR, MLR, PLR, SII, and CONUT scores were independent influences on patients' OS (all p values < 0.05). A nomogram (C-index 0.77, 95% CI: 0.71-0.84) was created based on these independent influences and later validated using a validation cohort (C-index 0.75, 95% CI: 0.68-0.81). The time-dependent receiver operator characteristic curve (ROC) showed that the area under curve (AUC) of the training cohort patients at 12, 18, and 24months was 0.72 (95% CI: 0.63-0.81), 0.75 (95% CI: 0.67-0.85), and 0.77 (95% CI: 0.66-0.87) and the AUC of the validation cohort was 0.69 (95% CI: 0.58-0.79), 0.74 (95% CI: 0.65-0.87), and 0.71 (95% CI: 0.64-0.89), respectively. Finally, calibration was performed using calibration curves, and the results showed that nomograms based on inflammatory metrics and CONUT scores could be used to assess survival (12, 18, and 24months) in patients with advanced BTC treated with ICIs in the first line. Patients with advanced BTC benefit more from first-line treatment with standard chemotherapy in combination with ICIs than with chemotherapy alone. In addition, nomograms based on inflammatory metrics and CONUT scores can be used to predict survival at 12, 18, and 24months in patients with advanced BTC treated with ICIs.

A Single-center Experience of Synchronous and Metachronous Hematologic and Oncologic Tumors

The incidence of cancer is increasing in the world. With the developments in cancer treatment, the life expectancy of patients is prolonged and the incidence of secondary malignancies is increasing. We retrospetively patients with syncronous / metachronous oncological malignancies accompanying hematological malignancies in a newly established hematology center. Data were obtained from the medical records. Demographic data, treatments and overall survival of the patients were evaluated. Twenty eight (6%) of 433 patients hematological malignancies were included in the study. 12 patients (42.9) were diagnosed with syncronous and 16 (57.1%) patients with metachronous hematologic-oncologic tumors. Sixteen of the patients were male,twelve were female. In syncronous tumors, the most common hematologic malignancy was Non-hodgkın lymphoma (NHL), while the most common oncologic malignancies were thyroid papillary cancer and colon cancer. In metachronous tumors, the most common malignancies were NHL and breast cancer. The median time between diagnosis of metachronous tumors was 49.5 months (8-192 months). The median survival of patients with syncronous malignancies was 19 months (SE=12.19) (95% CI 0-42.89), with metachronous malignancies was 22 months (SE=14.0) (95% CI 0-49.44). There was no statistically significant difference in the comparison of survival curves of patients with syncronous and metachronous malignancies (p=0.382). Oncological malignancies accompanying hematological malignancies are not uncommon. There is no standart treatment for syncronous / metachronous hematologic malignancies. In the presence of syncronous multipl malignancies should be evaluated individually.

Characteristics and clinical outcomes of patients with myeloid malignancies and DDX41 variants.

DDX41 is the most frequently mutated gene in myeloid neoplasms associated with germline predisposition including myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). We analyzed 3795 patients with myeloid neoplasms and identified 151 (4%) with DDX41 variants and a diagnosis of AML (n = 96), MDS (n = 52), and chronic myelomonocytic leukemia (n = 3). The most frequent DDX41 variants were the somatic variant p.R525H, followed by the germline variants p.M1I and p.D140fs. Most neoplasms had a normal karyotype (59%) and the most frequent co-mutations were TP53 (16%) and ASXL1 (15%). 30% of patients had no concomitant mutations besides DDX41 mutation. Patients with myeloid malignancies and DDX41 variants responded well to therapy, with an overall response rate for patients with treatment naïve AML and MDS of 87% and 84%, respectively. The median overall survival (mOS) of patients with treatment-naïve AML or MDS was 49 and 71 months, respectively. Patients with AML treated with low-intensity regimens including venetoclax had an improved survival (2-year OS 91% vs. 60%, p = .02) and lower cumulative incidence of relapse compared to those treated without venetoclax (10% vs. 56%, p = .03). In the 33% of patients receiving hematopoietic stem cell transplantation, the 2-year OS was 80% and 85% for AML and MDS, respectively.

HIPEC and PIPAC for gastric cancer: technique and comparison of efficacy. Literature review

Background: According to the World Health Organization (WHO) data, gastric cancer (GC) was the 5th most common cancer and the 4th leading cause of cancer death worldwide in 2020. Peritoneal metastases (PM) are associated with a poor prognosis and detected in 30 % of patients with locally advanced GC; the median overall survival in patients with PM is 3–6 months without any treatment and 6–12 months with the use of systemic chemotherapy. Delivery of appropriate chemotherapeutic drugs directly into the abdominal cavity increases the effectiveness of treatment without severe systemic side effects. Today, various forms of intra-abdominal chemotherapy of PM are used in the world.Aim: To evaluate the efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) and aerosol intraperitoneal pressure chemotherapy (PIPAC) in the treatment of GC PM.Purposes: To review current domestic and foreign publications on HIPEC and PIPAC, to compare their efficacy.Materials and methods: Articles in PubMed, Scopus, Web of Science databases were studied and analyzed for the key queries: “stomach cancer”, “carcinomatosis”, “peritoneal metastases”, “HIPEC”, “PIPAC”.Conclusions: The best results were achieved when using PIPAC as preoperative chemotherapy, followed by cytoreductive surgery in combination with HIPEC. Both procedures are promising and require further study with multicenter randomized prospective trials to assess their therapeutic potential.

Pelvic insufficiency fractures and pelvic bone metastases after neoadjuvant (chemo)radiotherapy for rectal cancer

Background: Pelvic insufficiency fractures (PIFs) are a late complication of radiotherapy for pelvic malignancies. We evaluated the incidence, radiologic findings, clinical course, and outcome of PIFs in patients treated with neoadjuvant (chemo)radiotherapy ((C)RT) for rectal cancer. Material and methods: Data of patients diagnosed with rectal cancer from a large teaching hospital treated from 2002 to 2012 were extracted from the Dutch Cancer Registry. All hospital records were reviewed for the diagnosis of PIFs or pelvic bone metastases. An expert radiologist reassessed all imaging procedures of the lower back, abdomen, and pelvis. Results: A total of 513 rectal cancer patients were identified of whom 300 patients (58.5%) were treated with neoadjuvant (C)RT (long- vs. short-course radiotherapy: 91 patients [17.7%] vs. 209 [40.7%], respectively). Twelve PIFs were diagnosed initially according to hospital records and imaging reports of all 513 patients. These 12 patients were treated with neoadjuvant (C)RT. After reassessment of all pelvic imaging procedures done in this patient group (432 patients (84.2%)), 20 additional PIFs were detected in patients treated with neoadjuvant (C)RT, resulting in a 10.7% PIF rate in irradiated patients. One PIF was detected in the group of patients not treated with neoadjuvant (C)RT for rectal cancer. This patient had palliative radiotherapy for prostate cancer and is left out of the analysis. Median follow-up time of 32 PIF patients was 49 months. Median time between start of neoadjuvant (C)RT and diagnosis of PIF was 17 months (IQR 9–28). Overall median survival for patients with PIF was 63.5 months (IQR 44–120). Conclusion: PIFs are a relatively common late complication of neoadjuvant (C)RT for rectal cancer but are often missed or misdiagnosed as pelvic bone metastases. The differentiation of PIFs from pelvic bone metastases is important because of a different treatment and disease outcome.

A Novel Nomogram for Identifying the Patients at Risk for Rapid Progression of Advanced Hormone-Sensitive Prostate Cancer.

The goal of this study was to assess the prognostic impact of the lower urinary tract symptoms (LUTS) in advanced prostate cancer (PCa) patients before progression to castration-resistant prostate cancer (CRPC). A retrospective analysis of the follow-up data for 152 CRPC patients was performed. Severe LUTS symptom was defined as an International Prostate Symptoms Score (IPSS) ≥20 at baseline. Cox regression analysis was conducted to assess CRPC prognostic factors. Nomogram model was created and assessed using the concordance index (C-index), calibration curves, receiver operating characteristic (ROC) curves, and decision curve analyses (DCA). The median CRPC free survival of patients with severe LUTS was 20.5 months, significantly longer than that (7.5 months) of less symptomatic patients. Furthermore, severe LUTS, the hemoglobin, albumin, lymphocyte, and platelet (HALP) score, and Gleason sum were determined to be independent prognostic markers and combined to establish a nomogram, which performed well in the customized prediction of CRPC progression at 6th, 12th, 18th and 24th month. The C-index (0.794 and 0.816 for the training and validation cohorts, respectively), calibration curve, and ROC curve all validated the prediction accuracy. DCA curve showed that it could be effective in helping doctors make judgments. The Nomogram-related risk score separated the patients into two groups with notable progression differences. Severe LUTS was significantly associated with decreased risk for rapid progression to CRPC. The developed nomogram could help identify patients who are at a high risk of rapid CRPC progression and provide tailored follow-up and therapeutic advice.

Establishment of a novel survival assessment and prediction model for advanced gastric cancer patients receiving immunotherapy.

Currently, there are only a few risk assessment tools that provide predictions of survival duration for patients with gastric cancer (GC) receiving immunotherapy. The purpose of the present study was to develop and validate a nomogram that uses statistical data to predict survival and make risk assessments for patients with advanced staged GC. A total of 1,013 patients consisting of a development cohort (n=501) and validation cohort (n=512) collected during the time interval between January 2018 and June 2022 were included in the present study. The analysis consisted of the discrimination index, calibration plots and decision curve of the nomogram model. A total of 167 (33.33%) patients from the development cohort, and 158 (30.85%) from the validation cohort died during the observation period. The median overall survival (OS) of female patients was higher at 980 days (95% CI, 613-NA) compared with that of male patients, which was 748 days (95% CI, 597-NA; P=0.24). The median survival of patients with domestic immunotherapy was 789 (95% CI, 597-NA) days, which was lower compared with the imported immunotherapy group who had a median OS of 980 days (95% CI, 582-NA; P=0.22). A total of four independent predictors, age (HR=1.012; P=0.0245), histological grade (HR=1.395; P=0.016), immunotherapy cycles (HR=0.932; P=0.028) and line of first immunotherapy (HR=1.693; P=0.0003), were identified. The C-index was 0.64 and 0.67 for the development and validation cohorts, respectively. Patients who received more cycles of immunotherapy as the first-line treatment with highly differentiated tumor led to increase in the survival time of the patients. Thus, this nomogram could be used to determine the benefit of immunotherapies on patients at various stages of treatment of GC.

What predicts survival in glioblastoma? A population-based study of changes in clinical management and outcome.

Glioblastoma is the most common and most aggressive primary brain tumor in adults. Despite multimodal treatment, the median survival time is 15-16 months and 5-year survival rate 5%-10%. The primary goal of this study was to identify prognostic factors for survival in an unselected population of patients operated for glioblastoma. The secondary goal was to explore changes in outcome and the clinical management of this patient group over time. We identified 222 consecutive adults operated for glioblastoma between November 2012 and June 2016 at the Department of Neurosurgery, Sahlgrenska University Hospital in Gothenburg, serving a health care region in the western part of Sweden with 1.900.000 inhabitants. Clinical variables were identified and tested as predictors for prognosis in extended Poisson regression models. The results were compared with a previously published cohort from 2004 to 2008, before current standard of care based on molecular tumor diagnosis was fully implemented. Median overall survival was 1.07 years, which was significantly longer than in the 2004-2008 cohort (1.07 vs. 0.73 y, age- and sex adjusted HR = 1.89, p < 0.0001). Variables associated with longer survival in the multivariable model were MGMT promoter hypermethylation, non-central tumor location, complete resection of enhancing tumor, WHO performance status 0-1, unilateral tumor location, fewer lobes involved, younger age and no comorbidities. The median survival for patients with glioblastoma treated according to current standard treatment has moderately but significantly increased, with MGMT promoter hypermethylation as the strongest predictor for survival.

Retrospective evaluation of our patients diagnosed with advanced pancreatic cancer

Aims: Pancreatic cancer attracts attention with its increasing frequency among gastrointestinal cancers. It has the worst prognosis of all cancer types. In this study, we aimed to retrospectively evaluate the clinical features and treatment results of our patients with advanced pancreatic cancer. Methods: In this study, 131 patients diagnosed with advanced pancreatic cancer and admitted to the Ankara Numune Training and Research Hospital Medical Oncology Polyclinic between November 2002 and January 2014 were retrospectively analyzed. Demographic characteristics of the patients, smoking, family history, basal CEA and basal CA 19-9 levels, treatment modalities, metastasis sites, progression-free survival, and overall survival times were evaluated. Results: The study population consisted of 131 patients, including 94 males and 37 females. Twenty of the patients were in the locally advanced stage, and 111 were in the metastatic stage. The median age of the patients was 60 years. 53.4% of the patients were smokers, and the median amount of smoking was 30 packs/year. Adenocancer was the most common histopathological subtype. The median basal CEA and Ca 19-9 levels were high at the time of diagnosis. Neoadjuvant chemotherapy was given to all locally advanced patients. The most commonly used chemotherapy regimens were single-agent gemcitabine and gemcitabine-cisplatin combination therapies. While 10 of the locally advanced patients received local treatment (chemotherapy or surgery) after neoadjuvant chemotherapy, the remaining 10 patients could not receive local treatment. The median overall and progression-free survival times were found to be significantly longer in patients with locally advanced disease who received local treatment after neoadjuvant chemotherapy [(18 months vs. 6.5 months; p=0.008), (11.3 months vs. 6.4 months; p=0.05)]. The most common site of metastasis in our patients with metastatic pancreatic cancer was the liver (80%). Cisplatin-gemcitabine was preferred as a KT regimen in 63.4% of metastatic cases. The median overall survival time of the patients in the metastatic stage was 8.1 months, and the median progression-free survival time was 5.7 months. The median progression-free survival of all patients included in the study was 6.2 months, while the median overall survival was 8.8 months. Conclusion: The median overall survival of patients with locally advanced pancreatic cancer was significantly longer compared to metastatic patients (18 months vs. 8.1 months; p=0.028). Progression-free survival and overall survival of patients with locally advanced disease who received or did not receive local treatment after neoadjuvant chemotherapy were found to be significantly longer in patients who received local treatment. (11.3 months vs. 6.4 months; p=0.05) (18 months vs. 6.5 months; p=0.008). Response rates of patients with metastatic pancreatic cancer; It was 49% in the gemcitabine-cisplatin combination arm and 30% in the single-agent gemcitabine arm.