Tumor Volume Research Articles

Prognostic Modeling of Overall Survival in Glioblastoma Using Radiomic Features Derived from Intraoperative Ultrasound: A Multi-Institutional Study

Background: Accurate prognostic models are essential for optimizing treatment strategies for glioblastoma, the most aggressive primary brain tumor. While other neuroimaging modalities have demonstrated utility in predicting overall survival (OS), intraoperative ultrasound (iUS) remains underexplored for this purpose. This study aimed to evaluate the prognostic potential of iUS radiomics in glioblastoma patients in a multi-institutional cohort. Methods: This retrospective study included patients diagnosed with glioblastoma from the multicenter Brain Tumor Intraoperative (BraTioUS) database. A single 2D iUS slice, showing the largest tumor diameter, was selected for each patient. Radiomic features were extracted and subjected to feature selection, and clinical data were collected. Using a fivefold cross-validation strategy, Cox proportional hazards models were built using radiomic features alone, clinical data alone, and their combination. Model performance was assessed via the concordance index (C-index). Results: A total of 114 patients met the inclusion criteria, with a mean age of 56.88 years, a median OS of 382 days, and a median preoperative tumor volume of 32.69 cm3. Complete tumor resection was achieved in 51.8% of the patients. In the testing cohort, the combined model achieved a mean C-index of 0.87 (95% CI: 0.76–0.98), outperforming the radiomic model (C-index: 0.72, 95% CI: 0.57–0.86) and the clinical model (C-index: 0.73, 95% CI: 0.60–0.87). Conclusions: Intraoperative ultrasound relies on acoustic properties for tissue characterization, capturing unique features of glioblastomas. This study demonstrated that radiomic features derived from this imaging modality have the potential to support the development of survival models.

Effectiveness and safety of hypofractionated gamma knife radiosurgery for large meningiomas and those adjacent to the optic pathway and brainstem: preliminary therapeutic outcomes.

Recent technologic advancements have facilitated the use of hypofractionated Gamma Knife-based radiosurgery (HF-GKRS) to treat large lesions or those in eloquent areas. This study aimed to analyze the preliminary results of HF-GKRS for these meningiomas, and to determine its effectiveness and safety.This single-center retrospective study analyzed data of patients who underwent HF-GKRS for large meningiomas or those in eloquent areas with > 6 months of follow-up. The primary outcome was progression-free survival (PFS). The secondary outcomes were neurological deterioration, post-treatment T2 signal changes following HF-GKRS, and tumor volume changes. Volumetric analysis of the tumors after treatment was also performed to assess changes in tumor size after HF-GKRS.Overall, 24 patients with a median follow-up period of 22 months (range: 6-49 months) were included. Among them, 18 (75%) patients had tumors in close proximity to the optic pathway, and 15 (63%) patients had large lesions (> 10 cm3). The cumulative 1- and 3-year PFS rates were 100% and 92%, respectively. The cumulative 3-year rate of adverse radiation effects was 9%. Overall, 12 patients (50%) showed tumor reduction, with a median tumor reduction rate of 45% (range: 25-58%).Our preliminary results revealed that HF-GKRS for large meningiomas or those in eloquent areas is safe and effective, with satisfactory short- and mid-term PFS and low adverse radiation effects. Further research with more patients and longer follow-up periods is required.

Recurrence Patterns and Management after Pleurectomy Decortication for Pleural Mesothelioma.

We hypothesize that recurrence following pleurectomy decortication (PD) is primarily local. We explored factors associated with tumor recurrence patterns, disease-free interval (DFI), and post-recurrence survival (PRS). Tumor recurrence is a major barrier for long-term survival after pleural mesothelioma (PM) surgery. All patients who underwent PD between 1998 and 2022 were identified. Patients with diffuse PM who achieved macroscopic complete resection and had sufficient information on tumor relapse were included. Postoperative scans were reviewed to determine the timing and sites of the first recurrence. A total of 436 patients had tumor recurrence during follow-up. Local recurrences occurred most frequently (N=370, 85%) and represented the only recurrence site in 29% (N=129) of cases. Patients with sarcomatoid tumors relapsed earlier than other subtypes (P=0.003) with more frequent distant spread compared to other subtypes (P<0.001). Multivariable analysis revealed that age (P=0.015), preoperative tumor volume (P<0.001), epithelioid histology (P<0.001), intraoperative chemotherapy (P<0.001), and TNM stage IV (P=0.003) were associated with DFI. Similarly, age (P=0.042), performance status (P<0.001), epithelioid histology (P<0.001), intraoperative chemotherapy (P<0.001), TNM stages III and IV (P=0.003 and 0.010 respectively), type of surgery (P=0.019), and number of recurrent lesions (P=0.024) were associated with PRS. Recurrence surgery (HR 0.46, 95% CI 0.29-0.74) and chemotherapy (HR 0.69, 95% CI 0.54-0.92) were independently associated with PRS in patients with distant with or without local recurrences. PM is frequently associated with local recurrence. Repeat surgical resection is feasible and can achieve good local control in selected cases.

Expanded Use of Vorasidenib in Non-Enhancing Recurrent CNS WHO Grade 3 Oligodendroglioma

Background/Objectives: Anaplastic oligodendrogliomas (AOs) are central nervous system (CNS) World Health Organization (WHO) grade 3 gliomas characterized by isocitrate dehydrogenase (IDH) mutation (m)IDH and 1p/19q codeletion. AOs are typically treated with surgery and chemoradiation. However, chemoradiation can cause detrimental late neurocognitive morbidities and an accelerated disease course. The recently regulatory-approved vorasidenib, a brain-penetrating oral inhibitor of IDH1/2, has altered the treatment paradigm for recurrent/residual non-enhancing surgically resected CNS WHO grade 2 mIDH gliomas. Though vorasidenib can delay the time to chemoradiation for grade 2 gliomas, the implications for vorasidenib in non-grade 2 mIDH gliomas are not well understood. Results: We present a case of a 71-year-old male with a grade 3 non-enhancing oligodendroglioma successfully treated with vorasidenib with an 11% reduction in residual tumor volume. Vorasidenib was well tolerated in our patient with a mild elevation in his liver transaminases that resolved following a brief interruption in treatment. Conclusions: Our case suggests that vorasidenib may impart therapeutic benefits in this setting. This case illustrates the need for further investigation into these less commonly addressed scenarios and treatment strategies that extend beyond current guidelines.

Macrophage-specific in vivo RNA editing promotes phagocytosis and antitumor immunity in mice

Macrophages play a central role in antitumor immunity, making them an attractive target for gene therapy strategies. However, macrophages are difficult to transfect because of nucleic acid sensors that can trigger the degradation of foreign plasmid DNA. Here, we developed a macrophage-specific editing (MAGE) system by which compact plasmid DNA encoding a CasRx editor can be delivered to macrophages by a poly(β-amino ester) (PBAE) carrier to bypass the DNA sensor and enable RNA editing in vitro and in vivo. We identified a four-arm branched PBAE with 1-(2-aminoethyl)-4-methylpiperazine end-capping (PBAE29) that enables highly efficient macrophage transfection. PBAE29-mediated transfection of cultured macrophages stimulated less inflammatory cytokine production and inflammasome activation compared with traditional lipofectamine or electroporation-mediated plasmid delivery. Transfection efficiency was further improved by delivering CasRx by minicircle plasmid. The MAGE system incorporated a layer of carboxylated-mannan coating to target macrophage mannose receptors and a macrophage-specific promoter for enhanced selectivity. The delivery of CasRx with guide RNA targeting the transcripts for sialic acid–binding immunoglobulin similar to lectin 10 and signal regulatory protein alpha expression resulted in effective protein knockdown, improving macrophage phagocytosis. The MAGE system also showed efficacy in targeting macrophages in vivo, stimulating antitumor immune responses and reducing tumor volume in murine tumor models, including patient-derived pancreatic adenocarcinoma xenografts in humanized mice. In sum, the MAGE system presents a promising platform for in vivo macrophage-specific delivery of RNA editing tools that can be applied as a cancer therapy.

KW2478 and Cisplatin Synergistically Anti-colorectal Cancer by Targeting PI3K/AKT/mTOR Pathway

Objective: The objective of this study is to examine the impact of KW-2478 combined with DDP on colorectal cancer cells both in vitro and in vivo and to elucidate the molecular mechanism of KW-2478 in colorectal cancer. Methods: qRT-PCR and Western blot were employed to assess HSP90 mRNA and protein expression in normal intestinal epithelial and colorectal cancer cells. DLD-1 and HCT116 were selected for the experiment. CCK-8 was used to detect cytotoxicity; apoptosis rate was measured using flow cytometry; Western blot was employed to measure the expression levels of apoptotic and PI3K/AKT/mTOR pathway proteins. HCT116 was used to construct a subcutaneous tumor model in nude mice. After treatment with KW-2478 and DDP, the growth rate, volume, and weight of the tumor were observed. The expression of Ki67 was detected by immunohistochemistry. Apoptosis of tumor cells was detected using TUNEL. Western blot was employed to measure the expression levels of apoptotic and PI3K/AKT/mTOR pathway proteins. Results: HSP90 mRNA and protein levels were elevated in colorectal cancer cells compared to normal colorectal epithelial cells. HSP90 mRNA and protein expression levels were also significantly elevated in HCT116 and DLD-1 cells compared to other colorectal cancer cells. In DLD-1 and HCT116 cells, KW2478 and DDP inhibited cell viability. The combination of KW2478 and DDP exhibited a significantly higher inhibitory effect compared to either KW2478 or DDP alone. DDP markedly triggered apoptosis in HCT116 and DLD-1. KW2478 at 3 μg/ml and 6 μg/ml induced apoptosis in HCT116 cells but not in DLD-1 cells. The combination of KW2478 and DDP induced a significantly higher apoptosis rate as compared to either KW2478 or DDP alone. Treatment of HCT116 and DLD-1 with KW2478 or DDP alone increased Bax, Caspase9, and Caspase3 protein expression, while decreasing BCL-2. The KW2478+DDP combined treatment group exhibited more significant changes. Phosphorylation of PI3k, AKT, and mTOR decreased in the KW2478 or DDP treatment groups, with more significant changes observed in the KW2478 + DDP combination group. The growth rate, volume, and weight of subcutaneous tumors in the KW2478 or DDP treatment groups were significantly lower than control, and the KW2478+DDP combination group was more affected. Ki67 expression in subcutaneous tumors was reduced in the KW2478 or DDP treatment groups compared to the vehicle control group, with the lowest expression observed in the KW2478 + DDP combination group. The fluorescence intensity of subcutaneous tumors was higher in both the KW2478 and DDP treatment groups compared to the vehicle control group, and the KW2478 + DDP combination group exhibited the strongest fluorescence intensity among them. Conclusion: The combination of KW2478 and cisplatin inhibits colorectal cancer cell proliferation and induces apoptosis by regulating the PI3K/AKT/mTOR pathway.

Simultaneous integrated boost to lateral pelvic lymph nodes during chemoradiotherapy in high-risk rectal cancer.

Preoperative chemoradiotherapy combined with total mesorectal excision (TME) is astandard treatment for locally advanced rectal cancer (LARC). However, lateral pelvic lymph nodes (LPLNs) are often inadequately treated with standard regimens. This study examines the treatment and postoperative outcomes in LARC patients receiving asimultaneous integrated boost (SIB) for LPLNs during long-course chemoradiotherapy. This retrospective study included high-risk LARC patients (UICC, "Union Internationale Contre le Cancer", stageIII) treated with preoperative chemoradiotherapy and SIB to LPLNs. Radiotherapy was delivered to the primary tumor and elective volumes with 50.4 Gy in 28fractions, and anSIB with amedian dose of 60.2 Gy was administered to clinically positive LPLNs. TME quality and postoperative complications were assessed using MERCURY and Clavien-Dindo, respectively. Time-to-event data were analyzed according to Kaplan-Meier. Between 2019 and 2023, 27patients with high-risk LARC and LPLN metastases were treated with chemoradiotherapy. After amedian follow-up of 19months, 2‑year overall survival was 80%, disease-free survival 80%, and local control of dose-escalated lymph nodes 100%. Three patients were managed nonoperatively after aclinical complete response on endoscopy and imaging. Of the 22patients who had surgery, only one had complications higher than Clavien-DindogradeI; TME was graded as MERCURYI in 73%. The SIB approach for LPLNs in LARC is feasible, does not increase postoperative morbidity, and achieves excellent local control. This study supports the consideration of dose-escalated radiotherapy for LPLNs to address high local recurrence risks.

Prognostic and Predictive Values of F-18 FDG PET/CT Volumetric Parameters in Small Cell Lung Cancer

Introduction: Volumetric parameters of the 18F-FDG PET/CT can contribute to the treatment decision in high risk patients. In the present study, we aimed to examine the predictive, prognostic, and clinical value of PET/CT by using the two volumetric parameters: metabolic tumor volume (MTV) and total lesion glycolysis (TLG), SUVmax to concurrently evaluate survival data in patients diagnosed with small cell lung cancer (SCLC). Methods: 244 patients with SCLC, who underwent 18F-FDG PET/CT imaging for staging purpose were enrolled. Primary tumor SUVmax, MTV (40-70%) and TLG (40-70%) obtained from PET/CT were documented. Results: All lesions (n=244) showed 18F-FDG uptake, mean SUVmax of 19.74±8.71 [range (min – max) = 3.80 - 58.80]. SUVmax was significantly higher in tumors with diameters &gt; 2 cm compared to those with diameters ≤ 2 cm (p=0.000). The mean survival time was significantly shorter in patients with tumor diameter greater than 2 cm, locoregional LN involvement, distant nodal metastasis, or distant organ metastasis (p=0.019, p

Fe3O4-viral-like Mesoporous Silica Nanoparticle(Fe3O4-vMSN)-Sustained Release of Lenvatinib for Targeted Treatment of Hepatocellular Carcinoma

Background: Lenvatinib is an oral tyrosine kinase inhibitor that selectively inhib-its receptors involved in tumor angiogenesis and tumor growth. It is an emerging first-line treatment agent for hepatocellular carcinoma (HCC). However, there is no intravenous ad-ministration of Lenvatinib. Aims: This study aimed to construct nanocomposites that can efficiently support Lenvatinib and target liver cancer tissues and cells. Objective: In this study, ferric oxide-viral-like mesoporous silica nanoparticles-folic acid (Fe3O4-vMSN-FA) nanocomposites loaded with Lenvatinib were constructed, and their anti-hepatocellular carcinoma effects were evaluated. Methods: The hydrothermal method was used to synthesize ferric oxide (Fe3O4). Ferric ox-ide-viral-like mesoporous silica nanoparticles (Fe3O4-vMSN) were synthesized using a two-phase method. Then, Fe3O4-vMSN was modified with folic acid (Fe3O4-vMSN-FA) to better target tumor cells. Results: The experimental data showed that Fe3O4-vMSN-FA nanocomposites were suc-cessfully synthesized and could be loaded with Lenvatinib (Len@ Fe3O4-vMSN-FA). Fe3O4-vMSN-FA had good stability and biocompatibility, and it can release the loaded Len-vatinib faster in an acidic environment (pH 5.5). CCK8 assay and flow cytometry showed that HepG2 cells in the Len@ Fe3O4-vMSN group had the lowest cell viability and the high-est apoptosis rate, confirming the anticancer properties of Len@ Fe3O4-vMSN-FA in vitro. In addition, transwell experiments showed that the migration and invasion ability of HepG2 cells in the Len@ Fe3O4-vMSN-FA group were significantly inhibited. In vivo fluorescence imaging in mice confirmed the enhanced tumor-targeting ability of Fe3O4-vMSN-FA. The tumor volume of the Len@ Fe3O4-vMSN-FA group was significantly reduced, and there was no significant effect on body weight. Moreover, serum liver function index (ALT and AST) and HE staining showed that Len@ Fe3O4-vMSN-FA did not cause obvious damage to organ tissue. Conclusion: Len@ Fe3O4-vMSN-FA has a good anti-liver cancer effect. Fe3O4-vMSN-FA can be used as an alternative platform for MSCs for drug delivery, providing more options for cancer therapy.

OGFr overexpression exerts anti-hepatocellular carcinoma effects by activating P16 and P21 to inhibit proliferation and migration of HepG2 cells.

Hepatocellular carcinoma (HCC) is the sixth most common type of cancer and the second leading cause of cancer death worldwide [19]. Opioid growth factor (OGF) has been shown to exhibit antitumour potential, binding to OGF receptor (OGFr). Naltrexone (NTX), an OGFr antagonist, is considered as a potential anti-cancer agent. However, the specific mechanism of how OGFr acts on HCC cells is yet to be elucidated. HepG2 cells were inoculated into subcutaneous areas of nude mice's back (200 μL, 2.5×10⁷/mL) to establish HCC in vivo models. HepG2 cells were transfected with lentiviral plasmids containing short hairpin RNA (shRNA) targeting OGFr (sh-OGFr) or negative control shRNA (sh-NC), and OGFr over-expression (OE-OGFr) or over-expression negative control (OE-NC) plasmids. Subsequently, male BALB/c nude mice were randomized into Control, sh-NC, sh-OGFr, OE-NC, and OE-OGFr groups (n = 6). Measurement of tumour size weekly for four weeks, TUNEL staining for apoptosis, and immunohistochemistry were performed. In vitro, HepG2 cells were randomized into OE-NC, OE-OGFr, and OE-OGFr+NTX (100 μmol/L) groups, and sh-NC, sh-OGFr, sh-OGFr+sh-P21, and sh-OGFr+sh-P16 groups. Cell viability by CCK8 assay, cell proliferation by EDU staining, cell migration by cell scratch, and Western blot were performed. In vivo, sh-OGFr-transfected HepG2 cells increased tumour weight, volume, and Ki67 expression, decreased P21 and P16 expression, and did not affect apoptosis rate. But the effect of OE-OGFr in HepG2 cells was completely the opposite. In vitro, OE-OGFr inhibited HepG2 cells' viability, proliferation, and migration, and further NTX intervention reversed its inhibitory effects. The transfection of HepG2 cells with sh-OGFr+sh-P21 and sh-OGFr+sh-P16 further enhanced the cell proliferation and migration abilities compared to the sh-OGFr group. OGFr overexpression may inhibit HCC progression by activating P16 and P21 expression to inhibit cell proliferation and migration, thereby providing new potential targets for HCC treatment.

Exploring the Role of [68Ga]Ga-DOTAGA-IAC and Comparison of Its Diagnostic Performance with [18F]F-FDG PET/CT in Radioiodine Refractory Differentiated Thyroid Carcinoma.

Introduction: Integrin antagonist complex (IAC), a novel αvβ3 integrin antagonist peptidomimetic, has emerged as a promising agent for molecular imaging of tumor angiogenesis. This study evaluates the biodistribution and clinical efficacy of [68Ga]Ga-DOTAGA-IAC PET/CT in detecting radioiodine-refractory differentiated thyroid carcinoma (RAIR-DTC), comparing its diagnostic performance with [18F]F-FDG PET/CT. Materials and Methods: In this prospective pilot study, RAIR-DTC patients underwent whole-body imaging with [18F] F-FDG PET/CT, followed by [68Ga]Ga-DOTAGA-IAC PET/CT. Biodistribution patterns of [68Ga]Ga-DOTAGA-IAC were assessed. Lesions with abnormal, nonphysiologic tracer uptake (showing activity exceeding mediastinal blood pool) were considered positive for disease. Imaging findings were compared between the two modalities, and quantitative metrics, including SUVmax, metabolic tumor volume, and total lesion glycolysis, were analyzed statistically. Results: Among 30 patients with RAIR-DTC, [68Ga]Ga-DOTAGA-IAC PET/CT revealed predominant physiological tracer uptake in the kidneys. [18F]F-FDG PET/CT identified 97 lesions, predominantly nodal (73.2%), while [68Ga]Ga-DOTAGA-IAC PET/CT detected 34 lesions, 50% of which were nodal. Few patients exhibited multiple lesions with varying uptake grades, with 20% showing coexisting higher-grade lesions (grade II or above) on [68Ga]Ga-DOTAGA-IAC PET/CT. Conclusion: Angiogenesis imaging using [68Ga]Ga-DOTAGA-IAC PET/CT demonstrates limited sensitivity for lesion detection in patients with RAIR-DTC compared with [18F]F-FDG PET/CT. However, the potential of [68Ga]Ga-DOTAGA-IAC as a diagnostic tool for other cancers has been used in other cancers with positive imaging characteristics warranting further exploration.

Defining “Giant” Mediastinal Tumors: Proposal of a New Clinical–Radiological Classification and Case Report

Background/Objectives: Mediastinal tumors, regardless of their location, can grow to significant sizes, causing compression-related symptoms. The term “giant” mediastinal tumor is inconsistently defined in the literature. This study presents a new clinical–radiological classification (CRC) for mediastinal tumors and evaluates its applicability through a systematic review and a detailed case analysis of a giant thymolipoma. Methods: A systematic review of the literature from the past decade was conducted using PubMed to identify relevant studies on “giant” mediastinal tumors. The inclusion criteria focused on studies involving adult patients with documented tumor size and symptomatology. The review identified 22 studies, with most anterior mediastinal tumors classified as CRC 3 (81%), indicating “giant” tumors. Thymolipomas accounted for 58% of these cases. Tumor volume and weight correlated with symptom severity, guiding surgical approaches. The proposed CRC effectively standardized the definition of “giant” tumors. The case analysis of a 6.84 kg thymolipoma highlighted the challenges of surgical resection, confirming the importance of tailored surgical strategies for large tumors. Conclusions: The novelty of the study lies mainly in the new clinical–radiological classification (CRC) of mediastinal tumors. This classification integrates clinical presentation and cross-sectional imaging findings, offering a standardized framework for tumor reporting. In addition, it provides a precise definition of “giant” mediastinal tumors. The findings emphasize the need for early surgical intervention to prevent severe symptoms and complications. This study also showcases the largest enbloc-resected thymolipoma reported in the recent literature, supporting the utility of the proposed classification in clinical practice.

Evaluation of Medical Treatment Results in Patients with Giant Prolactinoma Who Previously Underwent Surgery or Not

In this single-center retrospective study, we aimed to evaluate the results of medical therapy as primary or secondary treatment following surgery and compare follow-up outcomes between the two approaches. Patients were grouped as medical therapy alone (Group M) and surgery plus medical therapy (Group S+M). Patients' demographics, such as age and gender, and age at the diagnosis were recorded. Differences between the pre-and post-treatment tumor size, prolactin (PRL) levels, Knosp grades, tumor response to treatment, improvement in hypofunctions, visual field, and biochemical control were recorded and compared between the two groups. A total of 41 patients diagnosed with giant prolactinomas were included in the study. Hypopituitarism was found in 82.93%, hypogonadism in 80.59%, GH deficiency in 51.22%, ACTH deficiency in 36.59%, and TSH deficiency in 41.46% of the patients. Visual field defects were found by 60.53%. Tumor volume at diagnosis was significantly higher in Group M (p 0.05). This study's results demonstrate no statistically significant difference between medical therapy alone and surgery plus medical therapy regarding the reduction of tumor volume and normalization of PRL values in patients with giant prolactinomas. Surgery should be reserved for severe compression conditions, and potentially unnecessary surgical approaches should be avoided.

Inhibitory effects of the combination of rapamycin with gemcitabine plus paclitaxel on the growth of pancreatic cancer tumors

We previously examined the antitumor effects of short interfering RNA nanoparticles targeting mammalian target of rapamycin (mTOR) in an orthotopic pancreatic cancer mouse model. We herein report the inhibitory effects of the mTOR inhibitor rapamycin on tumor growth in a novel established mouse model of pancreatic cancer using human pancreatic cancer cell line-derived organoids. Gemcitabine, 5-fluorouracil, and gemcitabine plus nab-paclitaxel are clinically used to treat advanced pancreatic cancer. In vitro assays showed that rapamycin strongly inhibited cell invasion, while gemcitabine, 5-fluorouracil, and gemcitabine plus paclitaxel primarily inhibited cell proliferation with minimal effects on invasion. In vivo mouse experiments demonstrated that rapamycin exhibited superior antitumor activity to S-1 (a metabolically activated prodrug of 5-fluorouracil) and another mTOR inhibitor, everolimus, while its efficacy was similar to that of gemcitabine plus paclitaxel (which was used instead of nab-paclitaxel due to concerns about allergic reactions in mice to human albumin) in a mouse model of pancreatic cancer using human pancreatic cancer cell line-derived organoids. Furthermore, the combination of rapamycin with gemcitabine plus paclitaxel exerted synergistic inhibitory effects on the growth of pancreatic cancer tumors. Although the inhibition of tumor growth was significantly stronger in everolimus-treated mice than in control mice, there were no additive anti-growth effects when combined with gemcitabine plus paclitaxel. The present results suggest that the combination of rapamycin with gemcitabine plus paclitaxel achieved the greatest reduction in tumor volumes in the mouse xenograft model and, thus, has significant clinical promise.

Staging of prostate Cancer with ultra-fast PSMA-PET scans enhanced by AI.

PSMA-PET is a reference standard examination for patients with prostate cancer, but even using recently introduced digital PET detectors image acquisition with standard field-of-view scanners is still in the range of 20min. This may cause limited access to examination slots because of the growing demand for PSMA-PET. Ultra-fast PSMA-PET may enhance throughput but comes at the cost of poor image quality. The aim of this manuscript is to evaluate the accuracy of AI-enhanced ultra-fast PSMA-PET for staging of patients with prostate cancer. A total number of 357 whole-body [68Ga]Ga-PSMA-11 PET datasets were included. Patients underwent two digital PET scans, one at standard and one at ultra-fast speed (table speed: 0.6-1.2mm/s vs. 50mm/s). A modified pix2pixHD generative adversarial network to enhance the ultra-fast images was trained with 286 datasets and evaluated with the remaining 71 datasets. The staging accuracy of ultra-fast PSMA-PET and AI-enhanced ultra-fast PET was compared with the reference standard PET separately for miTNM regions proposed by PROMISE V2.0. The AI-network significantly improved the visual image quality and detection rate in most miTNM regions compared with the non-enhanced image data (T: 69.6% vs. 43.5%, p < 0.05; N: 46.3% vs. 27.8%, p < 0.01; M1a 64.4% vs. 47.5%, p < 0.01; M1b: 85.7% vs. 72.1%, p < 0.01). However, improvement was not significant for the M1c category (42.9 vs. 28.6%, p > 0.05). Missed lesions had a smaller SUVmax and lesion size compared with detected lesions (exemplary for N: 9.5 vs. 26.5 SUVmax; 4 vs. 10mm). SUVmax values of lesions were significantly different in all miTNM regions between the ultra-fast and reference standard PET, but only in the T-region between the AI-enhanced and reference standard PET. The AI-based image enhancement improved image quality and region detection rates by a mean of 17.9%. As the sensitivity of synthetic PET for small and low-uptake lesions was limited, a potential clinical use case could be disease monitoring in patients with high tumor volume and PSMA uptake undergoing PSMA radioligand therapy. The improvement in detection rate of distant metastases was not significant. This indicates that more training data is needed to ensure robust results also for lesions that have lower appearance frequency. Future studies on accelerated PSMA-PET seem warranted.

Primary staging with 2[18F]-FDG-PET/CT and -PET/MRI and radiotherapy response evaluation with MRI in uterine cervical cancer: an interim analysis of a prospective clinical trial

BackgroundIn uterine cervical cancer (UCC), tumour staging is performed according to the 2018 International Federation of Gynecology and Obstetrics (FIGO) system, where imaging is incorporated, or the more generic Tumour Node Metastasis (TNM) classification. With the technical development in diagnostic imaging, continuous prospective evaluation of the different imaging methods contributing to stage determination is warranted. The aims of this interim study were to (1) evaluate the performance of radiological FIGO (rFIGO) and T staging (rT) with 2-fluorine-18-fluoro-deoxy-glucose (2[18F]-FDG)-positron emission tomography with computed tomography (PET/CT) and with magnetic resonance imaging (PET/MRI), compared to clinical FIGO (cFIGO) and T (cT) staging based on clinical examination and conventional imaging, in treatment-naïve UCC, and to (2) identify possible MRI biomarkers for early treatment response after radiotherapy.MethodsTen consecutive patients with newly diagnosed UCC from the prospective PRODIGYN (Prognostic and Diagnostic Added Value of Medical Imaging in Staging and Treatment Planning of Gynecological Cancer) study (ethical approval number 2022-04207-01; NCT05855941) were included. Study participants underwent 2[18F]FDG-PET/CT and -PET/MRI, and an additional MRI one week after radiotherapy. Agreement between rFIGO and cFIGO was analysed using Cohen’s kappa. Differences in rFIGO between 2[18F]FDG-PET/CT and -PET/MRI were evaluated with Wilcoxon signed ranks test, and added value of rFIGO for metastasis assessment was demonstrated with descriptive statistics.ResultsIn 2/10 patients, a higher stage was obtained with rFIGO compared to cFIGO, where presence of metastases led to upstaging. In 3/10, rFIGO was lower than cFIGO, and in 5/10 rFIGO and cFIGO were similar. Degree of agreement between rFIGO and cFIGO was poor, (κ = 0.091, p < 0.005) with 2[18F]FDG-PET/CT and (κ = − 0.010, p > 0.05) with FDG/PET/MRI). There was no significant difference between 2[18F]FDG-PET/CT and -PET/MRI for rFIGO (p = 0.18), or rT stage assessment (p = 0.32). MRI-derived tumour volume and apparent diffusion coefficient (ADC) were most affected on MRI one week after radiotherapy.ConclusionsOur results indicate that there is an added value of rFIGO staging with 2[18F]FDG-PET/CT and -PET/MRI compared to clinical examination and conventional radiology, for metastasis assessment in treatment-naïve UCC. In early treatment response evaluation with MRI, ADC and tumour volume may be predictive parameters of interest in future prognostic analyses.Trial registrationClinical Trials, NCT05855941. Registered 02 May 2023, https://clinicaltrials.gov/study/NCT05855941?term=NCT05855941&rank=1.

A comparative analysis of toxicity and treatment outcomes of adaptive radiotherapy and intensity-modulated radiotherapy in cervical cancer

Adaptive radiotherapy (ART) provides greater benefits than intensity-modulated radiotherapy (IMRT) regarding dosimetric outcomes in patients with cervical cancer. To investigate the clinical benefits of ART, we have collected data from 115 cervical cancer patients who underwent radical radiotherapy at our institution. Fifty-nine patients received a single course of IMRT. Fifty-six patients underwent offline ART, defined as the reduction of the gross tumor volume (GTV) by at least 30% after 30 Gy of radiotherapy, followed by a modified treatment plan for the second-stage. After treatment, 53 patients of ART group achieved a partial response (PR) or completement response (CR), resulting in an objective response rate (ORR) of 94.6% for the ART group, compared to 93.2% for the IMRT group. Patients in both groups exhibited no significant differences in acute toxicities. However, the incidence of chronic constipation was significantly higher in the IMRT group compared to the ART group (p = 0.021). With a median follow-up time of 27 months, the ART group experienced a higher mortality (10/56) than the IMRT group (6/59). However, the difference between the two groups was not statistically significant. In summary, ART may be advantageous in reducing the incidence of chronic constipation among patients with locally advanced cervical cancer, and both clinical prognosis and near-term survival are satisfactory.

Inhibition of growth and lung metastasis of breast cancer by pH-responsive methotrexate/curcumin-loaded chitosan-stabilized nanoemulsions

Chemotherapeutic agents are widely used to combat breast cancer. However, due to their non-selective biodistribution, their usage is associated with severe adverse effects on healthy tissues. In this study, a chitosan-stabilized nanoemulsion (CSNE) was prepared for the codelivery of curcumin (CUR) and methotrexate (MTX). The mean diameter and polydispersity index of CUR–MTX–CSNEs were 194.63 ± 6.7 nm and 0.27 ± 0.06, respectively. Modifying the nanoemulsion surface with chitosan decreased the drug release at pH 7.4 compared to pH 5.8. The MTT test demonstrated that CUR–MTX–CSNEs were more successful in reducing the cell viability of 4T1 cells than both bare formulation and free drugs. Moreover, compared to the free drug-treated group, a 2.6 times reduction of the relative tumor volume was witnessed in CUR–MTX–CSNEs-receiving mice. Histopathological studies confirmed a more substantial inhibitory effect on tumor growth and pulmonary metastasis of developed nanostructures than free CUR/MTX. While there was no noticeable toxicity in the vital organs of CUR–MTX–CSNEs-receiving mice, free drugs resulted in severe toxicity in the liver, kidney, lung and spleen. Overall, the pH-dependent drug release, improved anti-tumor activity and reduced organ toxicity suggest that CUR–MTX–CSNE may be promising in breast cancer therapy.

Comparative Analysis of Systemic Immune Responses and Metastatic Risks in Tumor Ablation: An Animal Study of Radiofrequency Ablation and Irreversible Electroporation with Immune Modulation.

This study aimed to compare systemic immune responses and metastatic effects induced by radiofrequency ablation (RFA) and irreversible electroporation (IRE) in murine tumor models. We assessed cytokine production, growth of treated and untreated metastatic tumors, and synergy with immune checkpoint inhibitors (ICIs). Hep55.1c murine hepatoma cells were implanted in C57BL/6N mice to establish primary tumors. In Experiment 1 (n = 50), RFA or IRE was applied to primary tumors, followed by CD8+ T cell depletion in some groups to assess anti-tumor immune responses. Experiment 2 (n = 45) tested RFA and IRE combined with anti-PD-1 therapy for enhanced abscopal effects. In Experiment 3 (n = 28), anti-IL-6 antibody was administered in IRE-treated mice to examine IL-6's role in secondary tumor growth. Tumor volumes and cytokine/chemokine levels were monitored. Both techniques induced significant CD8+ T cell-mediated anti-tumor responses, with abscopal effects observed in untreated secondary tumors. CD8+ T cell depletion abolished these effects, confirming their role in systemic tumor control. Anti-PD-1 therapy combination further suppressed secondary tumor growth. However, IRE uniquely elevated IL-6 and other inflammatory cytokines, unexpectedly accelerating secondary tumor growth. Administration of an anti-IL-6 antibody mitigated this effect, reducing secondary tumor progression. The results of this animal study indicate that both techniques promote systemic anti-tumor immunity, though IRE uniquely induces an inflammatory response that risks exacerbating micro-metastases through IL-6. Combining IRE with IL-6 blockade may offer a promising strategy for nonthermal tumor ablation therapies. Further studies are warranted to refine ablation-immune therapy combinations for optimal therapeutic outcomes.

The Effect of Denosumab on Pain and Radiological Improvement in Giant Cell Tumours of the Spine in the Acute Setting.

Retrospective Cohort Study. The current recommended treatment for Giant Cell Tumour (GCT) of the spine is en bloc excision. Denosumab is a monoclonal antibody reducing osteoclast activity that shows promising results when used as a neo - adjuvant treatment. However, the current literature remains limited. The purpose of this study was to assess the effect of denosumab on tumour characteristics and symptom relief in the acute phase of treatment of spinal GCT. We performed a retrospective review of 16 patients treated with denosumab as neo-adjuvant and stand - alone treatment. MRI and PET tumour characteristics were taken before and after treatment and patients were interviewed for subjective pain responses. Following treatment, all patients showed improvement of pain, of which 68.7% of patients were pain free with 43.75% noting improvement within 48hours. Mean relative volumetric reduction in tumour volume was 37.3% (P < .001). Eight patients showed high grade of Bilsky classification (Epidural spinal cord compression scale - ESCC) with seven of them showing significant improvement to low grade of ESCC (P = .016). Median baseline PET Standardised Uptake Value (SUV)max was 14.57 and post treatment was 4.8 (P < .001). This study provides necessary insight to the limited literature on the use of denosumab for spinal GCT in the acute phase. The clinical and radiographic responses observed demonstrate the critical role that neo-adjuvant denosumab has by reducing the tumour burden around critical adjacent neurovascular structures before eventual resection, significant pain improvement even with presence of fractured vertebra.