• Photon minibeam-based LATTICE radiotherapy for small and medium-sized tumors: A dosimetric planning study.
    1 week ago
    Lattice radiotherapy (LRT) is a spatially fractionated technique that delivers three-dimensional high-dose vertices within tumors. However, conventional LRT is constrained by geometric limitations when applied to small and medium-sized tumor volumes, primarily due to the large beam sizes that restrict optimal lattice pattern formation.

    This study aims to investigate a photon minibeam-based LATTICE radiotherapy (mini-LRT) approach designed to overcome the geometric limitations of conventional LRT and enable effective spatially fractionated treatment for small and medium-sized tumors adjacent to critical organs.

    Three brain cases and three lung cases, with clinical target volumes ranging from 12.34 cc to 40.88 cc, were presented for treatment planning comparison between conventional LRT and mini-LRT. A multi-collimator delivery strategy employing shifted slit patterns was implemented to achieve complementary spatial coverage. Dose calculation and optimization were performed using Monte Carlo simulations and solved via an iterative convex relaxation algorithm. Reference stereotactic body radiation therapy (SBRT) plans were generated for all six cases, and setup-error robustness analysis was performed for two representative cases using nominal and shifted dose-influence matrix scenarios.

    Mini-LRT produced denser lattice structures in all cases, generating 5-11 vertices compared to only 1-3 vertices achievable with conventional LRT. Vertex diameters were reduced from 15.0 mm to 3.0-4.0 mm, and vertex-to-vertex distances decreased from 25.0 mm to 12.5 mm. The lattice volume ratio ranged from 0.68% to 1.07% with mini-LRT. Organs at risk (OARs) dose reductions were observed in the evaluated cases, including reduced mean dose to brainstem, heart, and esophageal. Furthermore, mini-LRT achieved a higher peak-to-valley dose ratio (PVDR) ranging from 2.19 to 2.94, compared to 1.75-2.34 for conventional LRT. Reference SBRT plans achieved clinical target volume (CTV) D95 = 50 Gy in all cases but showed elevated D0.03cc to adjacent OARs in selected anatomically constrained cases. In the representative robustness analysis, worst-case setup-error scenarios showed modest PVDR degradation.

    This proof-of-concept dosimetric planning study suggests that photon minibeam-based LATTICE radiotherapy can generate compact spatially fractionated dose distributions in selected small and medium-sized tumors. Compared with conventional LRT, mini-LRT increased vertex density, reduced lattice volume ratio, and improved OAR sparing in the evaluated cases. Additional experimental validation, motion assessment, and larger patient studies are required before clinical translation.
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  • Real-World Outcomes of Radium-223 Therapy in Metastatic Castration-Resistant Prostate Cancer: Predictive Value of PSA Doubling Time and Enzalutamide Continuation.
    1 week ago
    Radium-223 dichloride (Ra-223) is an effective treatment for metastatic castration-resistant prostate cancer (mCRPC) with bone metastases. However, predictive factors associated with treatment efficacy remain unclear. This study evaluated prognostic factors associated with the efficacy of Ra-223 and investigated outcomes according to enzalutamide (ENZ) combination patterns.

    We retrospectively analyzed 34 patients with mCRPC treated with Ra-223 between 2016 and 2024. Progression-free survival (PFS) and overall survival (OS) were evaluated according to time to CRPC, pre-treatment prostate-specific antigen (PSA), PSA doubling time (PSADT), metastatic burden, and ENZ treatment patterns. Cutoff values were determined using the Contal-O'Quigley method. This study was approved by the Institutional Review Board of Gunma University (Approval No. 1662).

    The median time to CRPC, pre-treatment PSA level, and PSADT were 17 months, 6.2 ng/mL, and 2.2 months, respectively. Shorter time to CRPC (≤ 19 months), higher pre-treatment PSA (> 2.67 ng/mL), and shorter PSADT (≤ 2 months) were significantly associated with shorter PFS. Patients with ≥ 4 bone metastatic regions had significantly worse OS than those with ≤ 3 regions. Among the ENZ treatment patterns, continuous ENZ administration combined with Ra-223 was associated with significantly longer PFS than discontinuation of ENZ.

    Time to CRPC, pre-treatment PSA, and PSADT may represent potentially useful candidate markers for identifying patients more likely to benefit from Ra-223 therapy. Continued ENZ administration during Ra-223 therapy was associated with favorable PFS in selected patients; however, this finding should be considered exploratory and requires validation in larger cohorts.
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  • [Cellular Senescence in Hematological Malignancies: Pathogenesis and Traditional Chinese Medicine Treatment Strategies--Review].
    1 week ago
    Cellular senescence is fundamentally characterized as an irreversible cell cycle arrest state. Studies have revealed that cellular senescence plays a significant role in the pathogenesis and progression of hematological malignancies. Consequently, inducing cellular senescence has emerged as a therapeutic strategy for these malignancies. Traditional Chinese herbal medicine, characterized by its high efficacy and relatively low toxicity, has shown unique potential in inducing senescence in hematological tumor cells. Previous studies have shown that traditional Chinese herbal medicine can induce cellular senescence through mechanisms such as telomere shortening, DNA damage induction, and regulation of the senescence-associated secretory phenotype (SASP) to treat hematological malignancies. This review aims to summarize the recent advances in the mechanisms by which cellular senescence contributes to the pathogenesis of hematological malignancies and the role of traditional Chinese herbal medicine in inducing cellular senescence for therapeutic purposes, thereby providing novel insights and theoretical support for the application of traditional Chinese herbal medicine in the treatment of hematological malignancies.
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  • [Clinical Characteristics, Drug Resistance, and Prognosis Analysis of Enterobacteriaceae Bloodstream Infection in Children with Acute Leukemia].
    1 week ago
    To investigate the clinical characteristics, drug resistance and prognosis of Enterobacteriaceae bloodstream infection (BSI) in children with acute leukemia (AL) following chemotherapy.

    A retrospective analysis was performed on children with Enterobacteriaceae BSI after AL chemotherapy in four hospitals in Fujian Province from January 2015 to December 2023. The clinical characteristics, drug resistance and prognosis of these children were analyzed.

    A total of 140 children were enrolled, including 117 cases of acute lymphoblastic leukemia and 23 cases of acute myeloid leukemia. BSI occurred in 52.14% of the children during the induction chemotherapy phase, 35.00% during the intensive chemotherapy phase, and 12.86% during the maintenance chemotherapy phase. All children manifested fever, 81.43% had neutropenia, 21.43% had septic shock, 16.43% had no clear infectious lesions, 83.57% had infectious lesions, and 45.71% had two or more multi-site infections. Among the 140 strains of Enterobacteriaceae bacteria, 50.71% were Klebsiella bacteria, 35.00% were Escherichia bacteria, 10.00% were Enterobacter bacteria, and 4.29% were Salmonella bacteria. The highest proportion of multidrug-resistant bacteria (MDRB) and carbapenem-resistant Enterobacteriaceae (CRE) were found in Escherichia (68.89% and 14.89%). Amikacin had the lowest resistance rate among Klebsiella, Escherichia, and Enterobacter. There were no significant differences in pathogen distribution, proportions of MDRB and CRE between the first 4 year group (2015-2018) and the last 5 year group (2019-2023) (P >0.05). There were significant differences in albumin levels, the proportion of anti-infective treatment one week before BSI, proportion of carbapenem anti-infective treatment before BSI, and proportion of deaths between CRE group and non-CRE group (all P <0.05). Among the 140 children, except for 2 children who gave up treatment and the outcomes were unknown, 123 children were cured and 15 children died of BSI. The attributable mortality rate was 10.87% (15/138), and the mortality related to septic shock was 33.33% (10/30). Univariate analysis showed that gender, proportion of septic shock, proportion of CRE strain, albumin level, C-reactive protein (CRP) level and procalcitonin level were significantly different between the cure group and the death group (all P <0.05). Multivariate logistic regression analysis showed that septic shock, lower albumin level and higher CRP level were independent risk factors for death in children with Enterobacteriaceae BSI.

    In children with Enterobacteriaceae BSI following AL chemotherapy, CRE infection is associated with higher mortality. Septic shock, low albumin, and high CRP are independent risk factors for death caused by Enterobacteriaceae BSI.
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  • [Predictive Value of a Risk Assessment Model Based on Coagulation Biomarkers for Venous Thromboembolism after Hematopoietic Stem Cell Transplantation in Children with Acute Lymphoblastic Leukemia].
    1 week ago
    To construct a risk assessment model for venous thromboembolism (VTE) in children with acute lymphoblastic leukemia (ALL) after transplantation, and to explore the value of this new model in predicting the risk of post-transplant VTE in children with ALL.

    A total of 113 children with ALL who underwent allogeneic hematopoietic stem cell transplantation (HSCT) at Children's Hospital of Soochow University were enrolled. According to the occurrence of VTE within 30 days after transplantation, the children were divided into VTE group and non-VTE group. Differences in the levels of coagulation markers and the distribution of other thromboembolism-related clinical risk factors were compared between the two groups. Logistic regression analysis was used to screen independent risk factors for post-transplant VTE. Based on these factors, a new VTE risk assessment model was established, and receiver operating characteristic (ROC) curves were plotted to evaluate the predictive performance of the new model for VTE in children with ALL after transplantation, as well as to compare its advantages over traditional methods.

    In the VTE group, the plasma levels of tissue plasminogen activator-inhibitor complex (t-PAIC), thrombin-antithrombin complex (TAT), plasmin-α2-plasmin inhibitor complex (PIC), prothrombin time (PT), activated partial thromboplastin time (APTT), and D-dimer (DD) were significantly higher than those in the non-VTE group, while the fibrinogen (FIB) level was significantly lower (all P < 0.05). In the VTE group, the duration of ALL was generally longer, and the detection rates of granulocytopenia, agranulocytosis, and peripherally inserted central catheter (PICC)-related bloodstream infection (CRBSI) were significantly higher than those in the non-VTE group (all P < 0.05). Multivariate analysis showed that t-PAIC >4.3 ng/ml (OR =30.19, P =0.005) and APTT >31.8 s (OR =12.17, P =0.015) were independent risk factors for post-transplant VTE in children with ALL. A new VTE risk assessment model was established based on these two risk factors. The model showed significantly superior performance in predicting post-transplant VTE in children with ALL compared with individual coagulation and fibrinolysis indicators, as well as the traditional Caprini score and DIC score, with an AUC of 0.90 (P =0.001).

    The novel thrombotic marker t-PAIC has important clinical value in the early prediction of VTE in children with ALL after HSCT. Compared with the traditional thrombosis risk assessment models, the new model established based on t-PAIC and APTT exhibits superior diagnostic performance and clinical applicability in the pediatric ALL population.
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  • [Validation of the Predictive Ability of IMWG, IMPEDE and SAVED Thrombosis Risk Stratification Systems for Venous Thromboembolism in Chinese Multiple Myeloma Patients].
    1 week ago
    To validate the predictive ability of the International Myeloma Working Group (IMWG) venous thromboembolism (VTE) scoring system, the IMPEDE VTE scoring system, and the SAVED scoring system for VTE in Chinese multiple myeloma (MM) patients.

    A total of 415 patients with MM who visited The First Affiliated Hospital of Soochow University from January 1, 2019 to June 30, 2023 were included in the research cohort, and a retrospective analysis of their data was conducted. These patients were scored according to the IMWG, IMPEDE, and SAVED thrombosis risk models, respectively, and the predictive value of these three scoring models for VTE events was evaluated.

    The cumulative incidence of VTE events was 7.0% in the 415 patients. Both the IMWG score and the IMPEDE score demonstrated predictive value for VTE events. Each 1-point increase in the IMWG score was significantly associated with VTE events after treatment initiation (HR=3.41, 95%CI : 2.48-4.69, P < 0.001). Similarly, each 1-point increase in the IMPEDE score was also significantly associated with VTE events after treatment initiation (HR=2.46, 95%CI : 1.95-3.10, P < 0.001). In contrast, the SAVED score did not show significant predi- ctive value for VTE events in Chinese MM patients (P =0.693). However, according to the IMWG risk stratification, the vast majority of patients (97.3%) were classified into the high-risk group; in contrast, only 1 case (0.2%) was categorized into the high-risk group based on the IMPEDE risk stratification, indicating that these two risk stratification criteria are not suitable for Chinese patients. Therefore, patients were regrouped according to the IMWG score: ≤2 points as low-risk (163 cases), 3-4 points as intermediate-risk (214 cases), and ≥5 points as high-risk (38 cases); The 6-month cumulative incidence of VTE events in the high-risk group was 36.8%, which was significantly higher than that in the intermediate- and low-risk groups (P < 0.001, log-rank test). Patients were regrouped according to the IMPEDE score: ≤3 points as low-risk (265 cases), 4-5 points as intermediate-risk (131 cases), and ≥6 points as high-risk (19 cases); The 6-month cumulative incidence of VTE events in the high-risk group was 42.1%, which was significantly higher than that in the intermediate- and low-risk groups (P < 0.001, log-rank test).

    The IMWG score and the IMPEDE score have predictive value for VTE events in Chinese patients with MM, but restratification of patients based on these scores is required, while the SAVED score is not applicable to Chinese MM patients.
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  • [Analysis of Clinical Features of Newly Diagnosed Multiple Myeloma Complicated with Light Chain Amyloidosis].
    1 week ago
    To analyze the clinical characteristics of patients with multiple myeloma (MM) complicated with light chain amyloidosis (AL), particularly those with cardiac amyloidosis (CA), in order to provide evidence for early identification.

    Clinical data were retrospectively collected from 359 newly diagnosed MM patients at the First Affiliated Hospital of Soochow University from August 2017 to December 2023. Based on histopathological results, patients were grouped to compare the clinical characteristics between the multiple myeloma with amyloid light-chain (MM-AL) group and the multiple myeloma without amyloid light-chain (MM without AL) group, as well as between the cardiac involvement and non-cardiac involvement subgroups within the MM-AL cohort.

    MM-AL patients accounted for 19.5% (70/359), of whom 30.0% had cardiac involvement. Compared with the MM without AL group, the MM-AL group had a higher proportion of λ light chain type (65.7% vs. 45.0%), a higher proportion of frail patients (45.7% vs. 29.1%), a lower proportion of DS stage III (84.3% vs. 93.4%), fewer patients presenting with bone pain as the initial symptom (45.7% vs. 69.2%), and higher proportions of patients with heart failure (12.8% vs. 4.2%) and non-hypoproteinemia polyserositis (27.2% vs. 5.9%) (all P < 0.05). Electrocardiogram abnormalities (low voltage, pseudo-infarction) were observed only in the MM-AL group. Compared with those without cardiac involvement, MM-CA patients had a higher proportion of light chain type (47.6% vs. 18.4%), a higher proportion of congestive heart-failure at onset (33.3% vs. 4.1%), a higher incidence of major adverse cardiovascular events during treatment (33.3% vs. 2.0%), and significantly elevated levels of NT-proBNP and hs-TnT, as well as a higher incidence of electrocardiogram abnormalities (all P < 0.05). Multivariate analysis showed that non-hypoproteinemia polyserositis (OR =7.66, P < 0.001) and λ light chain type (OR =2.40, P =0.017) were independent risk factors for MM complicated with AL. In terms of cytogenetics, the proportion of high-risk cytogenetic abnormalities was lower in MM-CA patients compared with those without cardiac involvement (14.3% vs. 36.7%, P =0.047).

    Patients with MM complicated by AL present with distinct clinical and cytogenetic features. The presence of λ light chain type and non-hypoproteinemic polyserous effusions are independent risk factors. Electrocardiographic findings of low voltage and pseudoinfarction patterns are suggestive of early recognition of AL and cardiac involvement.
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  • [Multi Model Study and Clinical Decision Analysis of Early Death Risk Warning in Patients with Newly Diagnosed Multiple Myeloma Treated with Daratumumab].
    1 week ago
    To retrospectively analyze the early death of patients with newly diagnosed multiple myeloma (NDMM) treated with daratumumab, build a risk warning model and verify its clinical decision-making benefits.

    The clinical data of 112 NDMM patients treated with daratumumab combination therapy in Tangshan Gongren Hospital from June 2018 to June 2022 were retrospectively collected as the training set, and the clinical data of 78 NDMM patients who received daratumumab combination therapy in the same period were collected as the validation set. According to whether early death occurred during regular follow-up (OS <24 months), the patients were divided into early death group (26 cases) and non-early death group (86 cases). The differences of clinical data between the two groups were analyzed, and Kaplan-Meier survival curves were used to analyze the survival difference of patients with different efficacy. Univariate and multivariate Cox regression analysis were used to analyze the independent risk factors affecting early death of NDMM patients treated with daratumumab. A warning nomogram model for the risk of early death was established, and the predictive performance was analyzed by receiver operating characteristic (ROC) curve and verified internally.

    According to whether the efficacy of daratumumab treatment achieved partial response (PR), the patients were divided into <PR group (32 cases) and ≥PR group (80 cases). Kaplan-Meier analysis found that the median OS of both groups were not reached, while the OS of patients with efficacy ≥PR was significantly longer than that of patients with efficacy <PR (log-rank χ2=14.225, P <0.001). Multivariate Cox regression analysis showed that older age, R-ISS stage Ⅲ, elevated hs-CRP, and efficacy <PR were independent risk factors for early death in NDMM patients (all P <0.05), and a nomogram model for early death risk in NDMM patients was constructed. ROC analysis and DeLong test showed that the AUC of the nomogram model was 0.894(95%CI : 0.828-0.959), which was higher than that of each individual model, and the differences were statistically significant (all P <0.05). Internal and external validation showed that the nomogram model was stable and had a positive net benefit.

    The OS of NDMM patients who did not reach PR after daratumumab treatment can be affected. Daratumumab treatment early death risk warning model for NDMM has good efficacy, and can be targeted at high-risk population for intensive treatment to improve prognosis.
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  • [Impact of TP53 and MYD88 Mutations on Treatment Efficacy in Diffuse Large B-Cell Lymphoma].
    1 week ago
    To investigate the relationship between TP53 and MYD88 mutations and treatment efficacy in patients with diffuse large B-cell lymphoma (DLBCL) who received rituximab-based standard chemoimmunotherapy.

    The clinical data of 92 patients with newly diagnosed DLBCL who were treated in the Department of Hematology of the Huai'an No.1 People's Hospital and Yancheng No.1 People's Hospital from January 1, 2015 to December 30, 2023 were retrospectively analyzed. Chi-square test, univariate and multivariate logistic regression analyses were used to identify risk factors associated with treatment efficacy, and a predictive model was further established. Survival curves were plotted using the Kaplan-Meier method, and differences in survival between groups were compared by the log-rank test.

    Among the 92 patients, 71 (77.2%) achieved post-induction remission (remission group) and 21 (22.8%) did not respond to treatment (non-remission group). The proportions of patients with elevated lactate dehydrogenase (LDH) (P =0.022) and those with MYD88 mutation (P =0.021) were significantly higher in the non-remission group than in the remission group. Univariate analysis showed that LDH (OR =3.482, P =0.027) and MYD88 mutation (OR =3.175, P =0.024) were factors influencing treatment efficacy in DLBCL patients receiving chemoimmunotherapy. Multivariate analysis showed that TP53 mutation (P =0.031) and MYD88 mutation (P =0.010) were independent risk factors for poor treatment efficacy in DLBCL patients. A treatment efficacy prediction model for DLBCL was established based on TP53 and MYD88 mutations, with an area under the receiver operating characteristic (ROC) curve of 0.705. According to the novel predictive model, the enrolled patients were divided into high-risk and low-risk groups. Treatment efficacy analysis showed that the objective response rate (ORR) of the low-risk group was significantly higher than that of the high-risk group (92.3% vs. 66.0%, P =0.006), and the progression-free survival (PFS) and overall survival (OS) of patients in the high-risk group were significantly poorer than those in the low-risk group (PFS: P =0.024; OS: P =0.004).

    TP53 mutation and MYD88 mutation are independent risk factors for poor efficacy in DLBCL patients receiving first-line immunochemotherapy. The novel predictive model constructed based on these two mutations can identify patients with potential poor response to first-line chemoimmunotherapy, which may provide a reference for optimizing the first-line individualized treatment strategy for DLBCL.
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  • [Clinicopathological Characteristics of Follicular Lymphoma with a Predominantly Diffuse Growth Pattern].
    1 week ago
    To investigate the clinicopathological features, diagnosis, differential diagnosis, treatment, and prognosis of a patient with follicular lymphoma with predominantly diffuse growth pattern (DFL), in order to enhance understanding of this rare lymphoma variant.

    Clinical and pathological data of one patient with DFL were collected. A retrospective analysis was conducted on the patient's clinical manifestations, pathological morphological features, immunophenotype, molecular genetic changes, treatment, and follow-up outcomes. Relevant literature was also reviewed.

    The patient was a 43-year-old female, presenting with a right inguinal area of more than four years' duration. Gross pathological examination revealed a single lymph node measuring 4.0 cm×3.0 cm×2.0 cm, with a gray-white, solid, and soft cut surface. Microscopic evaluation demonstrated architectural effacement and diffuse proliferation with focal residual indistinct follicular structures. Under high magnification, the tumor cells were predominantly centrocytes with a few scattered centroblasts in a heterogeneous background. Immunohistochemistry showed positive expression of CD10, BCL-6, and CD23 in tumor cells, but negative for BCL-2. STAT6 showed weak staining in <1% of tumor cells and was interpreted as negative. Fluorescence in situ hybridization (FISH) showed neither 1p36 deletion nor BCL2 rearrangement. Clonality analysis demonstrated clonal rearrangement of immunoglobulin genes, while T-cell receptor (TCR) gene rearrangement showed a polyclonal pattern. The patient underwent radiotherapy (24 Gy/12 fractions) to the right inguinal area, and has achieved complete remission to date.

    DFL is a rare subtype of follicular lymphoma with unique clinicopathological features and molecular genetic alterations, which may lead to diagnostic confusion with T-cell lymphomas. Accurate recognition of this subtype helps avoid misdiagnosis and inappropriate treatment. DFL is generally characterized by low histological grade, early clinical stage, and a favorable prognosis.
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