Intermediate-risk Patients Research Articles

Current insights on PSMA PET/CT in intermediate-risk prostate cancer: a literature review.

The purpose of this systematic review was to evaluate the role of PSMA PET/CT in intermediate-risk prostate cancer (PCa) patients, to determine whether it could help improve treatment strategy and prognostic stratification. A systematic literature search up to May 2024 was conducted in the PubMed, Embase and Scopus databases. Articles with mixed risk patient populations, review articles, editorials, letters, comments, or case reports were excluded. The quality of the papers was assessed by using the CASP criteria. The literature search returned 1111 studies; however, 1105 articles were excluded, and therefore 6 full-text papers were retrieved for the final analysis. Three out of six papers focused on the utility of SUVmax in identifying high ISUP grade in patients with intermediate-risk PCa. The latest three papers discussed the controversial role of PSMA PET/CT in predicting the lymph node involvement, mainly in the case of favorable subset. PSMA PET has completely changed the management of patients with PCa; indeed its role is still undefined in patients with intermediate-risk disease. Future perspective is to investigate larger cohorts of intermediate-risk PCa patients, to fully recognize the added value offered by PSMA PET in this category of subjects.

Real-world comparative outcomes and toxicities after definitive radiotherapy using proton beam therapy versus intensity-modulated radiation therapy for prostate cancer: a retrospective, single-institutional analysis.

This retrospective study aimed to compare the clinical outcomes of intensity-modulated radiation therapy (IMRT) and proton beam therapy (PBT). A total of 606 patients diagnosed with prostate cancer between January 2008 and December 2018 were included. Of these patients, 510 received PBT up to a dose of 70-78Gy (relative biological effectiveness) and 96 patients received IMRT up to a dose of 70-78Gy. The median follow-up period was 82months (range: 32-140months). Patients in the PBT group had significantly higher 7-year rates of biochemical relapse-free survival (bRFS) and disease-free survival (DFS) rates: 95.1% for PBT vs 89.9% for IMRT (P = 0.0271) and 93.1% for PBT vs 85.0% for IMRT (P = 0.0019). After matching analysis, 94 patients were assigned to both groups, and the PBT group showed significantly higher 7-year bRFS and DFS rates: 98.9% for PBT vs 89.7% for IMRT (P = 0.023) and 93.4% for PBT vs 84.6% for IMRT (P = 0.022), respectively. In the subgroup analysis of intermediate-risk patients, the PBT group showed a significantly higher 7-year bRFS rate (98.3% for PBT vs 90.5% for IMRT; P = 0.007). The V60 of the bladder in the PBT group (18.1% ± 10.1%) was higher than that in the IMRT group (14.4% ± 7.6%) (P = 0.024). This study found that the treatment outcomes of PBT potentially surpassed those of IMRT specifically concerning bRFS and DFS in real-world settings. However, it should be noted that attention is warranted for late bladder complication of PBT.

Prognostic significance of the mEPE score in intermediate-risk prostate cancer patients undergoing ultrahypofractionated robotic SBRT.

This study aimed to evaluate the prognostic significance of magnetic resonance imaging (MRI) parameters on biochemical failure-free survival (BFS) in patients diagnosed with intermediate-risk prostate cancer and treated with robotic ultrahypofractionated stereotactic body radiotherapy (SBRT) without androgen deprivation therapy (ADT). Aretrospective analysis was conducted in patients with intermediate-risk prostate cancer undergoing robotic SBRT delivered in five fractions with atotal radiation dose of 35-36.25 Gy. The primary endpoint was biochemical failure as defined by the Phoenix criteria. Among other clinicopathological data, Tstage, Prostate Imaging-Reporting and Data System (PI-RADS) score, and multiparametric magnetic resonance imaging-based extra-prostatic extension (mEPE) score were collected and analyzed using the log-rank test. Atotal of 74patients were eligible for analysis. Median age at treatment was 68.8 years and median prostate volume was 47.8cm3. Fifty-four and 14patients were diagnosed with Gleason scores 7a and 7b, respectively. In total, 40patients were classified as having unfavorable intermediate-risk prostate cancer according to American Urological Association/American Society for Radiation Oncology/ Society of Urologic Oncology (AUA/ASTRO/SUO) guidelines. The median follow-up was 30months (range: 4-91.2 months; interquartile range (IQR): 18.5-48months). The 3‑year BFS was 92%. Atotal of 12(16.2%) biochemical failures were reported. In univariate analysis, an mEPE score of 5, the delivered total radiation dose (35 Gy vs. 36.25 Gy), and aprostate-specific antigen (PSA) nadir >1 ng/ml were associated with lower BFS (mEPE-BFS: p < 0.001, total radiation dose-BFS: p = 0.04, PSAnadir-BFS: p =< 0.001). Patients diagnosed with intermediate-risk prostate cancer with ahigh mEPE score are more likely to experience biochemical failure after SBRT. Treatment intensification measures, such as administration of concomitant ADT, should be considered.

Real world experience of acute pulmonary embolism presented to a dedicated tertiary cardiac care center.

Objective: Pulmonary embolism is an uncommon disease with clinical presentation ranging from completely asymptomatic to hemodynamic instability and cardiopulmonary arrest. In this article we intend to highlight incidence, management and outcomes of disease in patient presenting to a tertiary cardiac center with acute pulmonary embolism. Study Design: Observational Cross-sectional study. Setting: Peshawar Institute of Cardiology, Peshawar. Period: 1st Sept, 2022 to 31st August 2023. Methods: All patients who underwent in-hospital Computed tomography pulmonary angiogram (CTPA), at out center. We collected data of all patient who were with CTPA proven pulmonary embolism via non-probability convenient sampling method. We accessed our local radiology and clinical databases for data collection. The collected data was integrated in SPSS version 23 for statistical analysis. Results: A total of 33 patients with CTPA proven pulmonary embolism were included out of which majority of patients were intermediate risk i.e., 20(71.4%). Management strategy used mainly was anticoagulation 27(81.8%). Regarding outcomes, 3(9.1%) expired while 30(90.9%) patients were discharged home successfully. Conclusion: Pulmonary embolism is not as uncommon as previously thought. A proper workup for its diagnosis and risk factors identification specially in young patients will not only improve management strategies but also quantify future risk of recurrence. Management of intermediate risk patient poses problems; this class of patients need strict monitoring for any clinical deterioration. Among these patients’ careful selection for thrombolysis to avoid deterioration has to be balanced with high risk of bleeding. In some high bleeding risk group catheter-based therapy may be an option.

High expression of EBP is an adverse prognostic factor for de novo acute myeloid leukemia

ABSTRACT Background: Acute myeloid leukemia (AML) is a heterogeneous disease, for which identifying reliable prognostic markers is critical for accurate clinical prognosis and treatment optimization. The inhibition of emopamil-binding protein gene (EBP) expression has been demonstrated to induce cancer cell death via depleting downstream sterols. Nevertheless, no comprehensive studies have been conducted specifically in tumors, including AML. Method: Herein, survival analyses were performed on the dataset obtained from The Cancer Genome Atlas (TCGA). Besides, the EBP levels were quantified using real-time qPCR in a cohort of 120 AML patients, and the value of EBP was further assessed using our clinical data. Results: Patients with high EBP expression had worse overall survival (OS) and event-free survival (EFS) than patients with low EBP expression, both in the TCGA dataset and our clinical data. Additionally, white blood cell (WBC) counts were higher in patients with high EBP expression (P = 0.032). Moreover, in patients with intermediate-risk AML, it was discovered that elevated EBP expression was linked to a worse EFS (P = 0.038). Multivariate analysis demonstrated that high EBP expression was an independent prognostic factor in AML patients and was associated with a shorter OS and EFS (OS: P = 0.041; EFS: P = 0.017). Furthermore, the data revealed that transplantation in the high-EBP group led to an improvement in survival (OS: P = 0.001; EFS: P = 0.001). The same benefit was also observed in intermediate-risk AML patients (OS: P = 0.026; EFS: P = 0.026). Conclusion: Collectively, our findings indicated that high expression of EBP in AML patients was an adverse prognostic factor, but transplantation had the otential to alleviate its negative effects.

Prognostic and therapeutic implications of measurable residual disease levels during remission induction of childhood ALL.

We evaluated the prognostic and therapeutic significance of measurable residual disease (MRD) during remission induction in pediatric acute lymphoblastic leukemia (ALL) patients. In the CCCG-ALL-2015 protocol, 7640 patients were categorized into low-, intermediate-, or high-risk groups based on clinical and genetic features. Final risk classification was determined by MRD assessed via flow cytometry on Days 19 and 46 of remission induction, with additional intensified chemotherapy for Day 19 MRD ≥1%. B-ALL patients with negative MRD (<0.01%) on Day 19 or Day 46 had significantly better 5-year event-free survival (EFS) than those with MRD 0.01-0.99%, who in turn had better EFS than patients with MRD ≥1%. Provisional low-risk patients with Day 19 MRD ≥1% but negative Day 46 MRD, reclassified as intermediate-risk, had comparable 5-year EFS to low-risk patients with Day 19 MRD 0.3-0.99% and negative Day 46 MRD (82.5% vs. 83.0%) and better EFS than provisional low-risk patients with MRD on both days (83.0% vs. 72.6%, P<0.001). Similarly, provisional intermediate-risk B-ALL patients with Day 19 MRD ≥1% but negative Day 46 MRD, who received additional therapy, had better 5-year EFS compared to those with Day 19 MRD between 0.3-0.99% (70.7% vs. 53.0%, P<0.001). Among low-risk patients with negative Day 46 MRD, those with negative Day 19 MRD had superior EFS compared to those with positive Day 19 MRD (91.7% vs. 86.1%, P<0.001). Optimal use of Day 19 MRD could improve individualized treatment and outcomes. Chinese Clinical Trial Registry (ChiCTR-IPR-14005706).

Integrated Use of Autosomal Dominant Polycystic Kidney Disease Prediction Tools for Risk Prognostication.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic cause of kidney failure. Specific treatment is indicated upon observed or predicted rapid progression. For the latter, risk stratification tools have been developed independently based on either total kidney volume or genotyping as well as clinical variables. This study aimed to improve risk prediction by combining both imaging and clinical-genetic scores. We conducted a retrospective multi-center cohort study of 468 patients diagnosed with ADPKD. Clinical, imaging, and genetic data were analyzed for risk prediction. We defined rapid disease progression as an estimated glomerular filtration rate (eGFR) slope ≥3 ml/min/1.73m2/year over two years, Mayo imaging classification (MIC) 1D-1E, or a Predicting Renal Outcome in Polycystic Kidney Disease (PROPKD) score of ≥7 points. Using MIC, PROPKD, and Rare Exome Variant Ensemble Learner (REVEL) scores, several combined models were designed to develop a new classification with improved risk stratification. Primary endpoints were the development of advanced chronic kidney disease (aCKD) stages G4-G5, longitudinal changes in eGFR, and clinical variables such as hypertension or urological events. Statistically, logistic regression, survival, Receiver Operating Characteristic (ROC) analyses, linear mixed models, and Cox proportional hazards models were used. PKD1-genotype (p <0.001), MIC class 1E (p <0.001), early-onset hypertension (p <0.001) and early-onset urological events (p =0.003) correlated best with rapid progression in multivariable analysis. While the MIC showed satisfactory specificity (77%), the PROPKD was more sensitive (59%). Among individuals with an intermediate risk in one of the scores, integration of the other score (combined scoring) allowed for more accurate stratification. The combined use of both risk scores was associated with higher ability to identify rapid progressors and resulted in a better stratification, notably among intermediate risk patients.

Integration of Genomic Tests in Prostate Cancer Care: Implications for Clinical Practice and Patient Outcomes.

Prostate cancer (PCa) is a common malignancy in men and is among the leading causes of cancer-related death worldwide. Genomic tests assess disease aggressiveness and guide treatment, particularly in low- and intermediate-risk PCa. We reviewed the literature on the use of four genomic tests (Prolaris®, Promark®, Oncotype DX®, and Decipher®) in assessing the prognosis of PCa and their use in treatment decision-making. Most of the studies showed that Prolaris® has a strong correlation with biochemical recurrence, metastasis risk, PCa-specific mortality (PCSM), and pathological features. Similarly, three studies on Promark® indicated a connection between results and pathological features in the subsequent prostatectomy, time to metastasis, and biochemical recurrence. Fourteen studies on Oncotype DX® showed a clear correlation between high scores, death, and PCSM. One study found that routine biopsy pathology reports, combined with serum PSA levels, provide a risk assessment comparable to Oncotype DX® testing. Results from 22 studies on Decipher® were controversial. The test was associated with conservative management, suggesting that patients with a high GC score are more likely to need radiation after surgery. Comparative studies indicated that Oncotype DX® is preferable for assessing PCSM, Decipher® for predicting metastasis, and Prolaris® for predicting recurrence. With the incidence rate of PCa dramatically increasing, genomic tests appear to be useful adjunctive precision medicine tools with significant potential in improving prognostic discrimination, facilitating better risk stratification, and guiding personalized treatment, especially in the intermediate-risk patient group. Large-scale, prospective, multi-sectional studies are required to validate the utility of these tests prior to their integration into clinical practice.

F18-DCFPyL PSMA-PET/CT Versus MRI: Identifying the Prostate Cancer Region Most at Risk of Radiation Therapy Recurrence for Tumor Dose Escalation.

Local recurrence of prostate cancer (PCa) after radiation therapy (RT) typically occurs at the site of dominant tumor burden, and recent evidence confirms that magnetic resonance imaging (MRI) guided tumor dose escalation improves outcomes. With the emergence of prostate-specific membrane antigen (PSMA) positron emission tomography (PET), we hypothesize that PSMA-PET and MRI may not equally depict the region most at risk of recurrence after RT. Patients with intermediate- to high-risk PCa and MRI plus PSMA-PET performed before RT were identified. The sextant most at risk of recurrence was defined as the pathologically dominant region with peak biopsy percentage core length involvement and any sextant with ≥ 40% percentage core length involvement (pathologic gross tumor volume [pGTV], per prior work). Imaging methods were reviewed independently to compare GTVs with pGTVs most at risk of recurrence. A paired chi-square test was employed for analysis. Eighty-eight patients (n = 88) were identified. Overall, there were no differences in the sensitivity of MRI and PSMA-PET for identifying the pGTV most at risk of recurrence. However, PSMA-PET demonstrated a trend of improved sensitivity for high-risk PCa compared with MRI (n = 46, 96% vs 87%, P = .06), while MRI outperformed PSMA-PET for the intermediate-risk group (n = 42, 93% vs 81%, P = .03). PSMA-PET showed lower specificity, misidentifying GTV in uninvolved pathologic sextants for 12% of intermediate-risk patients, whereas MRI was faultless (12% vs 0%, P = .03). MRI and PSMA-PET each misidentified uninvolved sextants for 9% of patients in the high-risk group. MRI demonstrates superior sensitivity in identifying the region most at risk of RT recurrence for intermediate-risk PCa, whereas PSMA-PET may add value for some high-risk patients. Informed by sextant biopsy information and MRI, clinicians should consider integrating PSMA-PET for patients with high-risk diseases when delineating GTVs.

Ladies project: large database in endometrial cancers for a personalized treatment.

To compare Italian use with current international guidelines and to evaluate oncological outcomes and toxicity patterns of adjuvant radiation therapy (RT) for endometrial cancer (EC) in Italian women. To conduct a retrospective multicentre Italian study a large database was set up. Inclusion criteria were: accrual between 2010 and 2020, treatment with surgery, post-operative external beam RT (EBRT) and/or interventional radiotherapy (IRT) associated or not with adjuvant chemotherapy. Oncological outcomes, acute and late toxicities were analysed according to RT schedule and risk group. A total of 1848 patients, from 16 Italian RT centres were enrolled (median age 65 years, range 27-88). All patients received post-operative RT associated with chemotherapy in 31%. Patients were stratified on the basis of standard risk factors (Bosse et al. in Eur J Cancer 51:1742-50, 2015). After merging intermediate and high-intermediate risk classes into one intermediate group and including advanced and oligometastatic disease in the high-risk group, the low-risk group encompassed 124 patients, the intermediate-risk 1140, and the high risk 576. No low-risk patient developed local relapse (LR). Multivariate analysis showed that intermediate risk patients had a 2.5-fold increased risk of LR if treated with IRT alone vs EBRT-IRT boost. RT schedule did not impact significantly on LR in high risk patients. All acute toxicity parameters were highest in patients who received EBRT with simultaneous integrated boost (EBRT-SIB) and lowest in patients who received only IRT (p < 0.0001). Late toxicity was highest patients who received EBRT-SIB and lowest in those who were given EBRT with sequential boost (p < 0.0001). This retrospective study showed that Italian administration of adjuvant RT for EC is in accordance with current international guidelines. IRT alone for low-risk patients and EBRT associated with vaginal IRT remain standard adjuvant approaches for EC.

Risk Stratification in Pulmonary Hypertension in the UAE

Risk stratification in pulmonary arterial hypertension is critical in determining therapeutic strategies for patients. Patients are stratified into low-, intermediate-, and high-risk groups based on determinants of prognosis like clinical assessment, exercise tests, biochemical markers, echocardiography, and haemodynamic tests. The primary objective of treatment is to shift each of the component tests into a low-risk zone either by treatment escalation alone, as in the case of intermediate-risk patients, or by a combination of treatment escalation and repeat evaluation by right heart catheterisation in high-risk patients. Low-risk patients should be clinically assessed at least every 3 months, but follow-up is more frequent for intermediate- and high-risk patients. Apart from improving survival rates, health-related quality of life is also assessed at baseline and followup visits, which may predict the prognosis. Additionally, therapeutic drug monitoring is also essential during visits due to the risk of major side effects during treatment initiation or dose escalation. Initial and follow-up risk stratification can prevent delays in the intensification of therapy, but insurance denials act as a barrier to this approach. Therefore, a dedicated insurance team is required for approval of testing and therapies and a fasttrack process to communicate with the pulmonary hypertension expert centre. It can be concluded that risk stratification improves the treatment approach and helps make individualised treatment decisions. It also helps healthcare professionals better allocate treatment resources in cases of scarcity.

Contact X-ray Brachytherapy (CXB) as a boost therapy after neoadjuvant (chemo)radiation in high-risk locally advanced rectal cancer.

Radical surgery following neoadjuvant therapy is the standard of care for locally advanced rectal cancer. A Contact X-ray Brachytherapy (CXB) boost can alternatively be used to treat residual disease post neoadjuvant (chemo)radiation, especially in patients who are not suitable for or do not wish to have surgery. Its role has mostly been studied to date in low to intermediate-risk patients. We have now evaluated the utility of CXB-boost in high-risk rectal cancers after their tumours have been significantly downstaged by neoadjuvant (chemo)radiation. Oncological outcomes and treatment tolerability were evaluated in 328 patients based on rectal cancer treatment risk stratification: low/intermediate risk (cT1-3ab, N0-1, M0, no extramural invasion (EMVI), mesorectal fascia (MRF) involvement >1mm) and high-risk (cT3cd-4/N2, M0, MRF≤1mm and/or EMVI positive). With median follow-up of 33(IQR:15-54) months and median age of 73(IQR:62-80) years, no significant differences were found between low/intermediate and high-risk groups in clinical complete response (78% vs 73%, p=0.32), local regrowth (16.6% vs 22.4%, p=0.41), nodal (1.8% vs 5.8%, p=0.051) or regional (1.3% vs 2.9%, p=0.33) relapse, or post-radiation toxicities (p=0.16). However, the high-risk group had a higher distant relapse rate (21.2% vs 10.7%, p=0.01), with no significant differences in 3-year organ preservation (80% vs 87%, p=0.25), 5-year disease-free (DFS) (62% vs 64%, p=0.46), or overall (OS) survivals (67% vs 64%, p=0.88). Longer treatment time, treatment gap >24 weeks between therapies, and administration of a higher than standard CXB dose were newly identified factors that negatively impacted outcomes. High-risk rectal cancer patients treated with CXB-boost had more distant relapses, but comparable locoregional tumour control, organ preservation, DFS and OS to lower-risk patients, with acceptable toxicities. CXB-boost is therefore a viable option for selected high-risk rectal cancer patients. Timely reassessment, prompt referral, and CXB dose optimisation are crucial for improving outcomes.

Optimizing the Treatment of Acute Promyelocytic Leukemia: A Maintenance-Free Strategy for Complete Remission

Background: Acute promyelocytic leukaemia (APL) is a distinct variant of acute myeloid leukaemia (AML), comprising 5-10% of all AML cases. Characterized by the t(15; 17) chromosomal translocation, APL presents a unique challenge due to its associated bleeding manifestations and coagulopathy, emphasizing the need for urgent and specialized management. Methods: This prospective open-label pilot study enrolled ten newly diagnosed APL patients, stratified based on the Sanz risk score. Low and intermediate-risk patients underwent ATRA+ATO induction therapy without chemo, followed by consolidation therapy. High-risk patients received additional single dose chemo Daunorubicin or Mitoxantrone alongside ATRA+ATO induction. The study evaluated patient characteristics, clinical findings, laboratory results, and treatment outcomes, focusing on complete remission (CR) after induction therapy and disease-free survival (DFS) at 3 years. Results: The study observed a 100% CR rate after induction therapy, with favourable 3-year DFS and event-free survival (EFS). No treatment failures, mortality, or relapses were reported. Laboratory findings and clinical outcomes were consistent with the characteristics of APL, including the hematological parameters. The absence of maintenance therapy minimized associated toxicities, supporting the safety and efficacy of the chemotherapy-free ATRA+ATO approach. Conclusion: This pilot study underscores the potential paradigm shift in APL management by demonstrating the safety and efficacy of a chemotherapy-free ATRA+ATO strategy. The results align with the 2023 National Comprehensive Cancer Network (NCCN) update, endorsing the ATRA+ATO regimen for APL. The on-going nature of the research emphasizes its contribution to evolving APL management practices, encouraging further comprehensive evaluations on a broader scale.

Risk stratification and diagnostic evaluation of patients found to have microscopic hematuria by their primary care providers.

Our goal was to identify, and risk stratify primary care patients with microscopic hematuria (MH), describe the diagnostic evaluations they received, and determine whether the evaluations were consistent with the recommendations of the 2020 AUA/SUFU microscopic hematuria guidelines. A retrospective review of patients presenting to primary care clinics with a diagnosis of MH was performed. The patient risk category was determined based on the 2020 AUA/SUFU guidelines. Diagnostic strategies were recorded, and guideline concordance was determined. Descriptive statistics were generated to describe outcomes. A total of 368 patients had a diagnosis of MH; 267/368 (72.6%) patients had all pertinent data available for risk stratification. One-hundred and fifty-six (58.4) patients were high-risk and 55 (35.3%) had a urologic visit. Forty-one of the 55 (75%) were diagnostically evaluated of which 13 (31.7%) were in-line with guideline recommendations. Eighty-two (30.7%) patients were at intermediate risk of which 33 (40.2%) had a urology visit. Of these 33 intermediate-risk patients, 27 (81.8%) were diagnostically evaluated, five (18.5%) of which were in-line with guideline recommendations. Twenty-nine patients were low risk of which 4 (13.8%) had a urology visit. Three of the four patients seen by urology (75%) were evaluated with imaging studies and none received a cystoscopy. Almost 60% of the patients in our cohort were high-risk according to the AUA/SUFU 2020 guidelines. Across all strata, the majority of patients lacked a urology visit and diagnostic evaluation consistent with guideline recommendations. Future efforts should ensure appropriate urologic referral and optimize initial diagnostic strategies for patients with MH.

Salvage Therapy Efficacy is Modified by Risk Group at Diagnosis in Patients With Relapsed Rhabdomyosarcoma.

Patients with relapsed rhabdomyosarcoma (RMS) are treated with varying approaches and have a poor overall survival (OS). We performed an observational comparison of salvage regimens exploring whether high-dose alkylator combinations were associated with longer OS. We categorized 110 patients with relapsed RMS from five institutions into two groups, those treated with regimens including a high-dose alkylator (Group A) and those treated without a high-dose alkylator (Group B). We compared OS between the two, adjusting for risk group at diagnosis and institution using Kaplan-Meier and Cox proportional hazards analyses. Median follow-up in the 32 survivors was 4years (range: 1.0-16.7years) with a 28% (95% CI: 19%-37%) 4-year OS. Group A patients had a longer OS compared to Group B (4-year OS 41%, 95% CI: 27%-58%, vs. 14%, 95% CI: 4%-24%, respectively, p = 0.002). Adjustment for risk group at diagnosis abrogated the association (HR 1.4, 95% CI: 0.8-2.3, p = 0.16), while controlling for institution had no effect. In stratified analyses, patients with low risk at diagnosis had the highest effect size, suggesting a benefit after high-dose alkylator regimens (stratified HR 4.4, 95% CI: 0.96-20.3, p = 0.06, reference Group A) compared to intermediate- (stratified HR 1.6, 95% CI: 0.9-3.2, p = 0.13) or high- (stratified HR 0.9, 95% CI: 0.4-1.8, p = 0.7) risk patients. Patients with relapsed RMS and low-risk group at diagnosis may benefit from high-dose alkylator chemotherapy, while the high-risk group has a dismal outcome regardless of treatment selection. It is inconclusive whether intermediate-risk patients may benefit from such therapy.

The role of high-dose methotrexate in T-cell acute lymphoblastic leukemia treatment: multicenter study results of ALL IC-BFM 2002 protocol

Backround. A progress in Tcell acute lymphoblastic leukemia (TALL) treatment has been achieved in recent years by use a combination of riskadopted chemoradiation therapy, based on highdose (5000 mg/m2) methotrexate. A prerequisite for successful therapy is carefully follow supportive care principles and recommendations, which include blood serum methotrexate concentration monitoring, leucovorin rescue and alkaline solutions use for the best methotrexate elimination and decrease its toxic effects.Aim. To assess the effectiveness of ALL ICFM 2002 protocol based on highdose methotrexate for Tcell acute lymphoblastic leukemia.Materials and methods. From 2003 to 2023 in retroprospective study 67 patients with primary diagnosed TALL were enrolled. Median age was 7.4 years (from 0 to 18 years). All the patients were treated according to riskadopted ALL ICFM 2002 protocol. The therapy efficacy was assessed by overall (OS), eventfree (EFS) and relapsefree survival analysis. The survival rates were calculated with statistic program SSS 21.0 by Kaplan–Meier method.Results. The use of highdose methotrexate for TALL treatment in ALL ICFM 2002 protocol secure high survival rates: 10‑year OS was 82.5 ± 3 %, EFS – 79.3 ± 3 %. Analyzing OS and EFS depending on prognostic risk group we found that standard risk patients had OS and EFS 85.4 ± 6.9 and 78.4 ± 8 %, intermediate – 85.6 ± 6.7 and 82 ± 7.3 % and highrisk – 34.6 ± 18.3 and 20.8 ± 17.1 % respectively (р &gt;0.05).Conclusion. ALL ICFM 2002 protocol for TALL includes highdose (5000 mg/m2) methotrexate is an effective for standard and intermediate risk patients, but for TALL patients with unfavorable prognostic factors it is necessary a therapy modification by additional cytotoxic and targeted options (nelarabine and daratumumab) inclusion and widening the indications for allogeneic stem cell transplantation.

The Evaluation of Radiolabeled Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography for Initial Staging in Intermediate-Risk Prostate Cancer Patients: A Retrospective Multicenter Analysis.

The aim of the present study was to assess the performance of radiolabeled-PSMA PET/CT in a cohort of intermediate-risk prostate cancer (PCa) patients for initial staging. This is a retrospective, multicenter analysis of patients diagnosed with intermediate-risk PCa who were staged using radiolabeled PSMA PET/CT to evaluate the extent of the disease before initiating appropriate treatment. The study included patients from the Nuclear Medicine Units of the Humanitas group between 2021 and 2024. The change in management due to the PSMA PET/CT examination was assessed. A total of 181 patients were enrolled across all three centers. Histopathological assessment from biopsy revealed that 51.4% of patients had favorable PCa, while 48.6% had unfavorable disease. PET/CT was positive for the primary lesions in all patients, but it revealed a positivity rate in 23 (12.7%) patients for nodes and distant organs, with a positivity rate of 0.21 in the unfavorable group and 0.05 in the favorable group (p < 0.005). Based on follow-up data, diagnostic accuracy was higher than 90% in both the favorable and unfavorable groups for lymph node and distant metastases. The inclusion of PSMA PET/CT in the diagnostic algorithm for patients with intermediate-risk PCa impacted patient management in 24 (13.3%) cases, based on the multidisciplinary team decision. PSMA PET/CT can affect the management of patients with intermediate-risk PCa in up to 13% of cases, mainly for unfavorable diseases. New imaging techniques as a first-line imaging procedure can help to plan the correct therapeutic approach in the intermediate-risk PCa group.

The increase in the expression of circRNAs may contributes to a poor prognosis in acute myeloid leukemia: A systematic review and meta-analysis.

The primary methods for defining the prognostic risk of AML patients are cytogenetic and molecular analysis at the time of diagnosis. However, the prognosis of intermediate-risk patients is still not well assessed for biomarkers. The main objective of this meta-analysis is to evaluate the relationship between circRNAs and AML prognosis, to provide a theoretical basis for finding effective prognostic indicators in intermediate-risk patients, and to provide an important scientific basis for the development or revision of WHO practice guidelines and ELN risk classification, and to highlight the importance of continuing to focus on and evaluate the prognostic impact of circRNAs on AML in future studies. We performed a comprehensive literature search across PubMed, the Cochrane Library, and Web of Science databases for studies published up to September 15, 2024. Articles were selected based on inclusion criteria. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of studies. The outcome measure of overall survival (OS) was used, and hazard ratios (HR) and 95 % confidence intervals (CI) were pooled to estimate the relationship between circRNA expression and prognosis in AML using STATA 17.0 software. A total of 13 studies involving 1401 AML patients were included. The studies showed a significantly increased hazard ratio (HR) of upregulated CircRNA expression for OS (HR=1.87, 95 % CI=1.51-2.32, P < 0.001). The results of subgroups analysis showed a significant increase in the hazard ratio (HR) for upregulation of CircRNA expression in EFS and circ_0012152（HR= 1.66, 95 % CI= 1.19-2.32, P < 0.005 and HR= 2.26,95 % CI= 1.27-4.00, P < 0.005), respectively. No significant heterogeneity or publication bias was detected. Upregulated circRNA expression is significantly associated with poor prognosis in AML patients and may serve as a prognostic marker for AML.

Survival prospects of pulmonary arterial hypertension associated with congenital heart disease: Insights from the HOPE registry.

Pulmonary arterial hypertension (PAH) is a severe complication among adult patients with congenital heart disease (ACHD). This study presents real-world data on risk stratification, pharmacotherapy and survival rates in PAH-ACHD. Data from PAH-ACHD patients were analyzed using The Hellenic Pulmonary Hypertension Registry (HOPE), spanning eight specialized centers between 2015 and 2023. Patients were categorized into low, intermediate, and high-risk groups using the ESC/ERS three-strata model to assess 1-year mortality risk. A total of 93 PAH-ACHD patients were included (median age 38.5years, 60.2% women). Most patients had an atrial septal defect (37.6%) or a ventricular septal defect (35.5%), with 11.8% presenting with complex ACHD. Eisenmenger syndrome was present in 35.5% of patients. The proportion of low-risk patients nearly doubled from first to last assessment (24.7% vs. 40.9%, p=0.001). Initially, 52.7% of patients were on PAH monotherapy, with a subsequent shift towards combination therapy (73.1%) during follow-up. Over a median follow-up of 5.9years, 29 patients (31.1%) died, with 1- and 5-year survival rates of 95.5% and 81.9%, respectively. Compared to the high-risk group, low- and intermediate-risk patients exhibited a 70% and 50% lower hazard of death, respectively. The lowest survival rates were observed in patients with Eisenmenger physiology. Survival prospects were favorable for the non-high risk patients in this nationwide cohort of PAH-ACHD patients. The observed shift towards combination therapy use may have contributed to the improvement in 1-year ESC mortality risk, underscoring the importance of timely combination therapy with PAH drugs.

High seroprevalence of CMV among Algerian hemodialysis patients and the general population: Intermediate-risk patients for post-transplant CMV infection.

Cytomegalovirus (CMV) is a virus of the herpesviridae family. CMV infection is associated with increased morbidity and mortality in immunocompromised subjects such as hemodialysis patients and transplant recipients. The aim of our study was to determine the serological status of potential kidney recipients and donors in order to assess the risk of post-transplant CMV infection and disease. We included 135 and 200 potential kidney transplant donors and recipients, respectively, who were tested for anti-CMV IgM and IgG by chemiluminescence on IMMULITE 2000 XPI®. The prevalence of anti-CMV IgG was 95.50% (95% CI [92.63%-98.37%]) in hemodialysis patients and 96.30% (95% CI [93.12%-99.48%]) in potential kidney donors. The difference between the two groups was not significant (p=0.721). Anti-CMV IgM were only detected in the sera of 13 hemodialysis patients and 3 healthy subjects. In both groups, the highest rate of anti-CMV IgG positivity was observed in subjects aged over 50years (100%), followed by those aged between 18 and 30years old, with a slightly higher seroprevalence in men than in women. Our results suggest a high prevalence of anti-CMV IgG in potential kidney donors and recipients (D+/R+), who could be classified as an intermediate risk group for post-transplant CMV infection and/or disease.