Tumor Volume Research Articles

Baseline PSMA PET/CT parameters predict overall survival and treatment response in metastatic castration-resistant prostate cancer patients.

Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease with varying survival outcomes. This study investigated whether baseline PSMA PET/CT parameters are associated with survival and treatment response. Sixty mCRPC patients underwent [18F]PSMA-1007 PET/CT before treatment with androgen receptor-targeted agents (ARTAs) or chemotherapy. Intensity-based parameters, volumetric parameters, metastatic sites and DmaxVox (distance between the two outermost voxels) from baseline PSMA PET/CT were collected, as well as age, Gleason score and laboratory parameters. Cox regression analysis evaluated their prognostic value for overall survival (OS). Additionally, a preliminary lesion-level analysis was done (n = 241 lesions) with lesion location and twelve radiomic features selected from previous literature. Logistic regression evaluated their association with PSMA PET/CT-based lesion progression after 3-4 months of treatment. Total tumour volume (PSMA-TV) (HR = 1.41 per doubling [1.17-1.70]), total lesion uptake (TL-PSMA) (HR = 1.40 per doubling [1.16-1.69]) and DmaxVox (HR = 1.31 per 10 cm increase [1.07-1.62]) were prognostic for OS, each independent of baseline PSA level (HR = 0.82 per doubling [0.68-0.98]), haemoglobin level (HR = 0.68 per mmol/L increase [0.49-0.95]) and line of treatment. On lesion-level, location (prostate vs bone OR = 0.23 [0.06-0.83]) and SUVmean (OR = 1.72 per doubling [1.08-2.75]) were independent prognostic markers for lesion progression, morphological and texture-based radiomic features were not. Baseline PSMA PET/CT scans have prognostic value in mCRPC patients and can potentially aid in treatment decision-making. DmaxVox can serve as a simpler alternative to PSMA-TV when automated segmentation software is not available. When combined with PSMA-TV, lower PSA levels indicated worse OS, which may be a marker of tumour dedifferentiation. Further research is needed to validate these models in larger patient cohorts. Question mCRPC is a highly heterogeneous disease, requiring good prognostic markers. Findings PSMA-TV was the best independent prognostic marker for OS; maximum distance between lesions (DmaxVox) can be used as a simpler alternative. Clinical relevance Baseline PSMA PET/CT parameters representing tumour burden were independently associated with OS in mCRPC patients, providing prognosticinsights for clinical decision-making. Although PSMA-TV was the best prognostic marker, DmaxVox can serve as an easier to obtain alternative.

Large language model-augmented learning for auto-delineation of treatment targets in head-and-neck cancer radiotherapy.

Radiation therapy (RT) is highly effective, but its success depends on accurate, manual target delineation, which is time-consuming, labor-intensive, and prone to variability. Despite AI advancements in auto-contouring normal tissues, accurate RT target volume delineation remains challenging. This study presents Radformer, a novel visual language model that integrates text-rich clinical data with medical imaging for accurate automated RT target volume delineation. We developed Radformer, an innovative network that utilizes a hierarchical vision transformer as its backbone and integrates large language models (LLMs) to extract and embed clinical data in text-rich form. The model features a novel visual language attention module (VLAM) to combine visual and linguistic features, enabling language-aware visual encoding (LAVE). The Radformer was evaluated on a dataset of 2985 patients with head-and-neck cancer who underwent RT. Quantitative evaluations were performed utilizing metrics such as the Dice similarity coefficient (DSC), intersection over union (IOU), and 95th percentile Hausdorff distance (HD95). The Radformer demonstrated superior performance in segmenting RT target volumes compared to state-of-the-art models. On the head-and-neck cancer dataset, Radformer achieved a mean DSC of 0.76 ± 0.09 versus 0.66 ± 0.09, a mean IOU of 0.69 ± 0.08 versus 0.59 ± 0.07, and a mean HD95 of 7.82 ± 6.87 mm versus 14.28 ± 6.85 mm for gross tumor volume delineation, compared to the baseline 3D-UNETR. The Radformer model offers a clinically optimal means of RT target auto-delineation by integrating both imaging and clinical data through a visual language model. This approach improves the accuracy of RT target volume delineation, facilitating broader AI-assisted automation in RT treatment planning.

Enhanced antitumor efficacy of nanostructured lipid carrier co-loaded with docetaxel and 5-fluorouracil for targeted gastric cancer therapy.

This study presents nanostructured lipid carrier (NLC) co-loaded with Docetaxel (DCT) and 5-Fluorouracil (5-FU) as a targeted therapeutic approach for gastric cancer (GC). Using nanoprecipitation, NLC-DCT/5-FU were synthesized and exhibited an average particle size of 215.3 ± 10.4nm, a polydispersity index (PDI) of 0.29, and a zeta potential of -17.1mV. Encapsulation efficiency reached 95.9% for DCT and 5-FU, with a loading efficiency of 11.2%. In vitro release studies demonstrated a biphasic release profile, with an initial burst and sustained release, achieving 85.6% DCT and 75.8% 5-FU release over 72h. Cytotoxicity assays in MKN45 cells showed a significantly lower half-maximal inhibitory concentration (IC50) for NLC-DCT/5-FU (0.3µM) compared to free DCT (3.9µM) and free 5-FU (19.5µM), indicating enhanced efficacy. In vivo evaluation in a GC mouse model confirmed substantial tumor volume reduction to 213 mm3 with NLC-DCT/5-FU treatment, compared to 432mm3 with the free-drug combination. Systemic safety assessment showed minimal adverse effects, suggesting the nanoparticles' enhanced therapeutic index. These results demonstrate that NLC-based co-delivery systems could substantially improve the clinical outcomes of GC therapy.

Quinacrine Inhibits Hepatocellular Carcinoma Growth and Enhances the Anti-HCC Effects of Lenvatinib.

Hepatocellular Carcinoma (HCC) is a highly prevalent cancer worldwide, necessitating effective treatment options. However, current treatments do not provide satisfactory results. Quinacrine, a synthetic drug belonging to the 9-aminoacridine family, has demonstrated promising antitumor effects. The objective of the current study is to evaluate the anti-HCC effect of Quinacrine and explore whether quinacrine can improve the anti-HCC response of lenvatinib in vitro and in vivo. The HepG2 and MHCC-97H cells were treated with Quinacrine. Cell proliferation and cell apoptosis were assessed using the Cell Counting Kit-8 (CCK8) Assay, Colony Formation Assay, and Annexin V/7-AAD staining method. The invasion and migratory ability of HepG2 and MHCC-97H cells were assessed by Transwell Assay. The level of ROS of HCC cells was measured using a ROS-kit by Flow cytometric analysis. Besides, an in vivo study was performed in the Balb/c nude mice bearing MHCC-97H tumors to analyze the function of Quinacrine in tumor growth. Quinacrine can decrease cell viability in HepG2 and MHCC-97H cells, but not affect LO2 cells. Quinacrine impaired the colony formation, invasion and migratory ability in half-maximal inhibitory concentration (IC50). Quinacrine also significantly induced apoptosis in HepG2 and MHCC-97H cells in a concentrationdependent manner. On the one hand, ROS was significantly up-regulated in HCC cells after quinacrine treatment. On the other hand, We found quinacrine blocked autophagy flux in HepG2 and MHCC-97H cells. Moreover, Quinacrine significantly enhances the anti-HCC efficacy of lenvatinib in vitro. In the mouse MHCC-97H model, We found that combination therapy with Quinacrine and lenvatinib resulted in a smaller tumor volume and weight than inoculated with lenvatinib alone. Our findings demonstrated that quinacrine exerts anti-HCC effects and sensitizes hepatocellular carcinoma to lenvatinib. Collectively, our study provides novel therapeutic insights for managing HCC and offers a valuable strategy for future clinical interventions in this field.

Evaluation of Anticancer Activity of Novel and Tumor-Targeted Glutamine-Conjugated Organotin(IV) Compounds in Colorectal Cancer─An In Vitro and In Vivo Study.

Over the years, numerous ligand-based organotin(IV) Schiff base compounds have shown remarkable cytotoxicity and anticancer activities, but their clinical use is restricted by systemic toxicity, prompting the search for targeted therapies. Targeted delivery can be enhanced by exploiting the inherent characteristics of cancer cells such as glutamine addiction, which is essential to support cellular biosynthesis and cell growth to sustain aberrant proliferation. Our previous study revealed glutamine-conjugated organotin(IV) compounds have strong DNA/protein affinities, favorable in silico ADME profiles, and significant antiproliferative activity. In this study, these compounds demonstrated significant cytotoxicity against human colon carcinoma and adenocarcinoma cell lines via the induction of cell cycle arrest and apoptosis. In DMH/DSS-induced experimental colon carcinogenesis, these compounds reduced tumor burden and volume and inhibited cell proliferation and induced apoptosis, with minimal toxicity. Tissue distribution studies revealed selective accumulation in the colon. These findings support their potential as chemotherapeutic candidates for colon cancer.

Prognostic value of serum cholinesterase and 18F-FDG PET/CT-derived metabolic parameters in non-small cell lung cancer patients: a retrospective cohort study.

The primary objective of this study was to explore the prognostic significance of serum cholinesterase (CHE) and metabolic parameters obtained from 18F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) scans in patients with nonsmall cell lung cancer (NSCLC). A retrospective observational cohort study was conducted with 202 NSCLC patients. Serum CHE was evaluated alongside metabolic tumor volume (MTV) and total lesion glycolysis (TLG) derived from PET/CT scans. The correlation between these parameters and overall survival (OS) was analyzed using log-rank tests, as well as univariate and multivariate Cox regression analyses. A nomogram prediction model was developed and assessed using time-dependent receiver operating characteristic curves, calibration curves, and decision curve analysis (DCA). High MTV (≥16) and TLG (≥108) were found to be significantly correlated with worse OS outcomes (both P < 0.001), whereas lower CHE levels (<6818) were associated with worse OS (P = 0.002). A multivariate analysis revealed that MTV, TLG, serum CHE, and the presence of distant metastasis were independent prognostic factors for OS. The nomogram prediction model, incorporating these variables, exhibited strong predictive performance, as indicated by area under the curve values of 0.826, 0.796, and 0.845 for 1-, 3-, and 5-year OS predictions, respectively. Calibration curves demonstrated good concordance between predicted and observed survival rates, and DCA confirmed clinical relevance. Serum CHE and 18F-FDG PET/CT metabolic parameters may serve as important prognostic indicators for patients with NSCLC. The integration of these factors into a nomogram prediction model can assist in clinical decision-making and patient risk stratification.

Tumour growth rate and invasive interval cancer characteristics in a UK breast cancer screening population.

To estimate tumour volume doubling time (TVDT) of interval cancers (ICs). Two radiologists retrospectively reviewed prior screening and diagnostic mammograms and measured mean diameter on "visible" ICs. Univariate analyses of clinicopathological variables (ER, HER2, grade, age at diagnosis, and breast density) were undertaken, and those with p < 0.1 were included in a generalised linear model to estimate TVDT, cancer size at screening, and time of cancer visibility for "non-visible" tumours. From 2011 to 2018, 476 ICs were diagnosed, almost half in the third year after screening with 86% grade 2 or 3. A visible abnormality at screening was identified in 281/476 (59%) cases. Significant differences in TVDT were found with age (p < 0.02), ER status (p < 0.0001). Median TVDTs of grade 1, 2 and 3 cancers were 317, 288, and 195 days, respectively (p < 0.001). For non-visible cancers, the median estimated size at screening was 1.7 mm (IQR 1.0-2.5) for grade 1, 2.5 mm (IQR 1.5-5.9) for grade 2, and 0.9 mm (IQR 0.4-2.0) for grade 3 cancers, p < 0.001. The estimated time for cancer visibility was 489 days (IQR 229-682) after screening and 645 days (IQR 527-798) for cancers diagnosed in the third year after screening. Using TVDT of retrospectively visible interval cancers, non-visible interval cancer sizes can be estimated at the time of screening. Increasing the frequency of screening from three-yearly to two-yearly invitations would reduce the number of interval cancers significantly. Question Growth modelling of visible interval cancers (ICs) at screening helps to track the likely progression of non-visible ICs over the screening interval. Findings Tumour doubling time of visible ICs at screening is positively associated with age and ER status and inversely associated with cancer grade. Clinical relevance Interval cancer characterisation and growth modelling can be helpful to better predict the benefits of supplemental screening and the frequency of screening, given a minimum detectable size.

A multi-modal deep learning model for prediction of Ki-67 for meningiomas using pretreatment MR images

This study developed and validated a deep learning network using baseline magnetic resonance imaging (MRI) to predict Ki-67 status in meningioma patients. A total of 1239 patients were retrospectively recruited from three hospitals between January 2010 and December 2023, forming training, internal validation, and two external validation cohorts. A representation learning framework was utilized for modeling, and performance was assessed against existing methods. Furthermore, Kaplan–Meier survival analysis was conducted to investigate whether the model could be used for tumor growth prediction. The model achieved superior results, with areas under the curve (AUCs) of 0.797 for internal testing and 0.808 for generalization, alongside 0.756 and 0.727 for 3- and 5-year tumor growth predictions, respectively. The prediction was significantly associated with the growth of asymptomatic small meningiomas. Overall, the model provides an effective tool for early prediction of Ki-67 and tumor volume growth, aiding in individualized patient management.

Sustainable Synthesis of Nitrogen-Embedded Cu2S Quantum Dots for In Vitro and In Vivo Breast Cancer Management.

The burgeoning field of nanomedicine is exploring quantum dots for cancer theranostics. In recent years, chemically engineered copper sulfide (Cu2S) quantum dots (QDs) have emerged as a multifunctional platform for fluorescence-based sensors with prominent applications in imaging and chemodynamic therapy of tumor cells. The present study demonstrates the sustainable synthesis of nitrogen-embedded copper sulfide (N@Cu2S) quantum dots for the first time and unveils their potential application in in vitro and in vivo breast cancer management. The N@Cu2S QDs were morphologically analyzed by using TEM, revealing an average particle size of 5.4 nm. Their crystalline phase, nitrogen embedding, and luminescence properties were further investigated with XRD, XPS, and PL spectrometers, respectively. The in vitro cytotoxicity studies revealed that N@Cu2S QDs effectively inhibited the proliferation of both human (MDA-MB-231) and mouse (4T1) breast cancer cells while not damaging normal mouse fibroblast (NIH/3T3) cells. Furthermore, the in vivo investigation showed a significant reduction in tumor volume with a tumor growth inhibition of 63.52% in QD-treated mice, which was further supported by bioluminescence and fluorescence tumor imaging. Additionally, the organ-specific histopathological analysis validated the safety profile of the N@Cu2S QDs. The robust anticancer properties and high biocompatibility of N@Cu2S QDs underscore their potential as a promising option for breast cancer therapy, paving the way for future clinical applications.

Communicating hydrocephalus following stereotactic radiosurgery for periventricular meningiomas: illustrative cases.

Stereotactic radiosurgery (SRS) is a well-established option for the management of intracranial tumors, including meningiomas. Although valued for its low invasiveness and precision, it still carries a risk of complications. Communicating hydrocephalus is a serious, albeit rarely reported, complication of SRS. Here, the authors report two cases of communicating hydrocephalus following Gamma Knife radiosurgery (GKRS) for periventricular meningiomas. In both reported cases, the patients experienced a sudden deterioration in their clinical condition a few months after the second GKRS for recurrent periventricular World Health Organization grade II atypical meningiomas. The patients underwent ventriculoperitoneal shunt implantation, and cerebrospinal fluid (CSF) samples revealed elevated levels of total protein and albumin. Additionally, both patients underwent multiple resections before radiation, and some of their lesions were located near the venous sinuses. Though rare, communicating hydrocephalus represents a significant potential sequela of SRS for meningiomas that clinicians should be aware of. Factors such as tumor volume and location, histology, and previous irradiation or surgery can exacerbate radiation-induced damage and collectively underlie the development of hydrocephalus. The authors also speculate that the CSF protein levels can serve as a unifying marker of SRS-induced radiation damage in the form of radiation-associated tumor necrosis, radiation-induced hyperpermeability, and inflammatory response. https://thejns.org/doi/10.3171/CASE24722.

The Estimation Value of 99mTc-MAA in Comparison with 90Y-PET/MR-based Dosimetry in Selective Internal Radiation Therapy (SIRT) for Liver Malignancies.

This study intended to compare the radiation dose estimates to target and nontarget liver compartments from 99mTc-MAA SPECT/CT and 90Y-PET/MR scans in liver tumors treated by 90Y-glass microspheres. Dose estimation was performed for twenty-three eligible patients (13M, 10F) after 99mTc-MAA simulation using SPECT/CT imaging, and over 90Y-PET/MR images after 90Y-microsphere therapy. Simplicit90Y™ software was used for voxel-based dosimetry over the liver parenchyma. Dose estimates were obtained for whole healthy liver (HL), healthy injected liver (HIL), and tumor volumes. Pearson correlation, Bland-Altman plot, and Wilcoxon signed-ranks test were used for statistical analysis. The mean tumor dose was 270±111 Gy, the whole liver parenchyma dose was 26 ±12 Gy, and the healthy injected liver dose was 55±18 Gy from 99mTc-MAA simulation. 90YPET/ MR dosimetry yielded a mean tumor dose of 271±125 Gy, a HIL mean dose of 54±18 Gy, and a liver parenchyma dose of 25±12 Gy. An excellent agreement was demonstrated between tumor doses (R2=0.90) and liver doses (R2=0.87), while the agreement was less for HIL doses (R2=0.80). Wilcoxon signed-ranks test yielded no significant difference between the dose estimates for all liver compartments. It was deduced that 99mTc-MAA SPECT/CT simulation provides valuable dose prediction in 90Y-glass microsphere therapy. Despite the difference in volume measurements and dose estimates with 90Y-PET/MR, the predictive value of the 99mTc-MAA simulation was not affected.

MicroRNA-129-3p Suppresses Tumor Progression and Chemoradioresistance in Head and Neck Squamous Cell Carcinoma.

(1) Background: MicroRNA-129 (miR-129) participates in tumor progression and chemoresistance in various cancer types. In this study, the role of miR-129-3p, the main mature form of miR-129, in tumor progression and chemoradiotherapy resistance in head and neck cancer was evaluated. (2) Methods: RT-PCR, western blotting, cell proliferation assays, cell apoptosis assays, and cell invasion and migration assays were used. (3) Results: In this study, the miR-129-3p overexpression suppressed the proliferation, invasion, and migration of SNU1041, SCC15, and SCC25 human HNSCC cell lines. Additionally, it induced apoptosis and enhanced radiation-/cisplatin-induced apoptosis of SNU1041, SCC15, and SCC25 cells. Therefore, miR-129-3p could suppress tumor progression and enhance chemoradiosensitivity in human HNSCC. Furthermore, miR-129-3p was downregulated in fresh tumor tissues from patients with HNSCC compared with that in the adjacent normal mucosa. In a nude mouse xenograft model with SNU15 cells, the miR-129-3p overexpression significantly decreased tumor growth, as measured by tumor weight and volume. (4) Conclusions: Our study provides evidence that miR-129-3p suppresses tumor progression and chemoradioresistance in HNSCC. This finding may serve as a basis for developing miR-129-3p-based therapeutic strategies.

Aggressive resection of non-contrast-enhanced tumor provides varying benefits to glioblastoma, IDH-wildtype patients based on different clinical characteristics.

Supramaximal resection in glioblastoma, concerning non-contrast-enhancing (nCE) tumors, exhibited additional survival benefits. However, whether all patients can benefit from supramaximal resection of nCE tumors and the optimal resection target remains unclear, especially for the glioblastoma, IDH-wildtype under the new WHO CNS tumor classification. Clinical and surgical characteristics were collected from 155 patients with newly diagnosed glioblastoma, IDH-wildtype from the Chinese Glioma Genome Atlas, and a prospective cohort of 128 patients was enrolled for external validation. Recursive partitioning analysis was used to identify risk groups considering the effects of residual nCE tumor volume (RnTV) and clinical factors on overall survival (OS). Age, preoperative Karnofsky Performance Score (KPS), MGMT promoter status, and postoperative RnTV were independently associated with patient survival. Four risk groups with distinct prognoses were identified: Group 1 (median OS: 13.4 months), RnTV >43.27ml; Group 2 (median OS: 17.8 months), RnTV ≤43.27ml, KPS ≤90, and age ≥60; Group 3 (median OS: 22.3 months), RnTV 5.27-43.27ml, age <60; Group 4 (median OS: 38.2 months) including 4a, KPS 100 and RnTV ≤43.27ml; and 4b, KPS ≤90, age <60, and RnTV ≤5.27ml. These results were retained regardless of MGMT promoter methylation status and validated in the external prospective validation cohort. Supramaximal nCE tumor resection enhances survival outcomes in glioblastoma, IDH-wildtype, but depending on clinical characteristics. In young symptomatic patients, supramaximal resection should be recommended with the RnTV ≤5.27ml; in symptomless patients or elder patients, keeping the RnTV ≤43.27 is recommended to obtain the survival benefit from tumor resection surgery.

Utility of 18F-FDG PET/CT metabolic parameters on post-transplant lymphoproliferative disorder diagnosis.

Using 18F-FDG PET/CT metabolic parameters to differentiate post-transplant lymphoproliferative disorder (PTLD) and reactive lymphoid hyperplasia (RLH), and PTLD subtypes. 18F-FDG PET/CT and clinical data from 63 PTLD cases and 19 RLH cases were retrospectively collected. According to the 2017 WHO classification, PTLD was categorized into four subtypes: nondestructive (ND-PTLD), polymorphic (P-PTLD), monomorphic (M-PTLD), and classic Hodgkin. Metabolic parameters included maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG) and at different thresholds of SUVmax (2.5 and 41%), as well as gross tumor volume (GTV) was also collected. Nonparametric test and receiver operating characteristic (ROC) curves were used for statistics. There were 42 ND-PTLD patients, 7 P-PTLD patients, and 14M-PTLD patients. Ki-67 was significantly correlated with all metabolic parameters (P all < 0.01). SUVmean, SUVmax, MTV, TLG and GTV were all highest in M-PTLD, followed by P-PTLD, ND-PTLD, and RLH. ROC curves showed 18F-FDG PET/CT metabolic parameters all had moderate diagnostic efficacy in differentiating between PTLD and RLH, the area under the curves (AUC) range from 0.682 to 0.747. Diagnostic efficacy for P-PTLD + M-PTLD showed excellent performance (AUC for RLH + ND-PTLD vs P-PTLD + M-PTLD was 0.848 for SUVmax, 0.846 for SUVmean41%, 0.834 for SUVmean2.5, and 0.819 for GTV). For MTV41%, TLG 41%, MTV2.5, TLG2.5, the AUC was 0.676, 0.761, 0.761, 0.787, respectively. 18F-FDG PET/CT metabolic parameters at different thresholds of SUVmax (2.5 and 41%) exhibited comparable diagnostic efficacy for PTLD and its subtypes. All metabolic parameters demonstrated moderate diagnostic efficacy in distinguishing PTLD and RLH. SUVmax, SUVmean41%, SUVmean2.5 and GTV showed excellent performance in diagnosing P-PTLD + M-PTLD.

Diffusion changes in minimally invasive parafascicular approach for deep-seated tumours: impact on clinical outcomes.

Minimally invasive parafascicular surgery (MIPS) with the use of tubular retractors achieve a safe resection in deep seated tumours. Diffusion changes noted on postoperative imaging; the significance and clinical correlation of this remains poorly understood. Single centre retrospective cohort study of neuro-oncology patients undergoing MIPS. The impact of surgical approach-transsulcal (TS) versus transgyral (TG) - and respective entry points in clinical and imaging outcomes was assessed. 82 patients (35 male; 47 female, average age 43.94 ± 22.85years) were included. 84% presented with neurological deficit and glioblastoma was the commonest diagnosis (38.24%). Surgical approach was not relevant for the number of patients that showed postoperative peritubular injury (TS: 20 (37.74%) versus TG: 8 (27.59%), p = 0.354) or its volume (TS: 0.95 ± 1.82cc versus TG: 0.43 ± 1.32cc, p = 0.1435). When adjusted for preoperative volume and depth of tumour, TS approach was associated with less diffusion restriction (p = 0.030). Temporal lobe access points had the highest volume of diffusion restriction (temporal lobe-2.50 ± 3.54cc versus frontal lobe - 1.15 ± 1.53 versus parietal lobe-0.51 ± 0.91cc, p = 0.0096), particularly in the TS approach (p = 0.0152). Superior motor outcomes were demonstrated in the TS versus the TG approach (postoperative improvement: TS: 14.63% versus TG: 6.9%, p = 0.015), especially for parietal approaches (p = 0.039). TS approach was related with a significantly decreased length of stay (TS-11.67 ± 14.19days versus TG - 23.97 ± 18.01days, p = 0.001). Transsulcal approach demonstrated abetter motor outcome profile, particularly in parietal lobe, and shorter length of stay. The superior temporal sulcus was more susceptible to ischaemic changes. Therefore, transgyral route can be considered in temporal lobe MIPS.

Chlorpyrifos induces lung metastases and modulation of cancer stem cell markers in triple negative breast cancer model.

Breast cancer is a major public health problem, and distant metastases are the main cause of morbidity and mortality. Chlorpyrifos is an organophosphate that promotes Epithelial-Mesenchymal Transition-like phenotype in breast cancer cell lines and modulates the Breast Cancer Stem Cells activating two key processes related to the metastatic cascade. Here, we investigated whether Chlorpyrifos may induce distant metastases in an in vivo triple negative tumor model. Also, we studied the expression of Breast Cancer Stem Cell and Epithelial-Mesenchymal Transition activation-markers in Triple Negative Breast Cancer mice tumors and human cells. We demonstrate that Chlorpyrifos modulates stem cell plasticity as a function of growth conditions in monolayer or three-dimensional culture. Furthermore, Chlorpyrifos decreased the doubling period, increased tumor volume, stimulated the infiltration of adjacent muscle fibers and induced lung and lymphatic node metastases in mice. Finally, Chlorpyrifos modulated the expression of Epithelial-Mesenchymal Transition and Breast Cancer Stem Cell markers in mice exposed to the pesticide. All our findings confirm that Chlorpyrifos promotes breast cancer progression, enhances stemness and Epithelial-Mesenchymal Transition marker expression and generates lung metastases in an in vivo model induced in mice.

Utilizing Patient-Derived Xenografts to Model Precision Oncology for Biliary Tract Cancer.

Biliary tract cancers, which are rare and aggressive malignancies, are rich in clinically actionable molecular alterations. A major challenge in the field is the paucity of clinically relevant biliary tract cancer models that recapitulate the diverse molecular profiles of these tumors. The purpose of this study was to curate a collection of patient-derived xenograft (PDX) models that reflect the spectrum of genomic alterations present in biliary tract cancers to create a resource for modeling precision oncology. PDXs were derived from biliary tract cancer samples collected from surgical resections or metastatic biopsies. Alterations present in the PDXs were identified by whole-exome sequencing and RNA sequencing. PDXs were treated with approved and investigational agents. Efficacy was assessed by change in tumor volume from baseline. Event-free survival was defined as the time to tumor doubling from baseline. Responses were categorized at day 21: >30% decrease in tumor volume = partial response, >20% increase in tumor volume = progressive disease, and any non-partial response/progressive disease was considered stable disease. Genomic sequencing demonstrated key actionable alterations across this cohort, including alterations in FGFR2, isocitrate dehydrogenase I, ERRB2, PIK3CA, PTEN, and KRAS. RNA sequencing demonstrated fusions and expression of antibody-drug conjugate targets, including TROP2, HER2, and Nectin4. Therapeutic matching revealed objective responses to approved and investigational agents that have been shown to have antitumor activity clinically. In this study, we developed a catalog of biliary tract cancer PDXs that underwent comprehensive molecular profiling and therapeutic modeling. To date, this is one of the largest collections of biliary tract cancer PDX models and will facilitate the development of personalized treatments for patients with these aggressive malignancies.

Comparison of 1D and 3D volume measurement techniques in NF2-associated vestibular schwannoma monitoring

To compare 1D (linear) tumor volume calculations and classification systems with 3D-segmented volumetric analysis (SVA), focusing specifically on their effectiveness in the evaluation and management of NF2-associated vestibular schwannomas (VS). VS were clinically followed every 6 months with cranial, thin-sliced (< 3 mm) MRI. We retrospectively reviewed and used T1-weighted post-contrast enhanced (gadolinium) images for both SVA and linear measurements. 3D-SVA was performed manually or combined with semiautomated segmentation by using axial planes. The maximum linear dimensions (MLD) were determined in three dimensions (anteroposterior, transverse, and craniocaudal planes) using axial and coronal planes. The MLD was cubed (MLD3), and orthogonal analysis (OA) was derived to establish comparability with the SVA. The Hannover and Koos classification was used to depict the size ratio in each MRI and tumor. A linear regression model was performed to compare 1D/classification systems to SVA, and the percentage deviation change of MLD3 and OA to SVA was established using a one-way multivariate variance analysis. 2586 SVA and 10344 linear measurements were performed in a cohort of 149 NF2 patients and 292 associated VS. All measurement techniques (MLD3, OA, KOOS, and Hannover) significantly (and strongly, r2 > 0.5) correlated with SVA (p < 0.001). The OA showed an even stronger positive correlation than the MLD3 to SVA. Smaller classified tumors (T1/T2, K1/K2) exhibited a low-moderate positive correlation (r2 = 0.23–0.44) compared to medium-sized (T3, K2/3) and large tumors (T4, K4; r2 = 0.54–0.76). Pre- and postoperative MLD3 and OA statistically significantly predict SVA (p < 0.001), but the postoperative correlation was weaker, particularly for MLD3 to SVA values. All analyses showed a large scatter range. In the percentage deviation analysis of MLD3 and OA from SVA, small tumors (K1/K2, T1/T2) were overestimated. Compared to the SVA, the MLD3 and especially the OA are a time-saving alternative for monitoring the tumor volume of NF2-associated VS. However, the scatter range in small/surgically reduced tumors is enormous. For this reason, they are not recommended for monitoring off-label therapy with Bevacizumab or for treatment decisions depending on a precise assessment of tumor volume and growth. Developing deep learning-based volume determinations in the future is essential to reduce SVA’s time intensity.

Prognostic value of manual versus automatic methods for assessing extents of resection and residual tumor volume in glioblastoma.

The extent of resection (EOR) and postoperative residual tumor (RT) volume are prognostic factors in glioblastoma. Calculations of EOR and RT rely on accurate tumor segmentations. Raidionics is an open-access software that enables automatic segmentation of preoperative and early postoperative glioblastoma using pretrained deep learning models. The aim of this study was to compare the prognostic value of manually versus automatically assessed volumetric measurements in glioblastoma patients. Adult patients who underwent resection of histopathologically confirmed glioblastoma were included from 12 different hospitals in Europe and North America. Patient characteristics and survival data were collected as part of local tumor registries or were retrieved from patient medical records. The prognostic value of manually and automatically assessed EOR and RT volume was compared using Cox regression models. Both manually and automatically assessed RT volumes were a negative prognostic factor for overall survival (manual vs automatic: HR 1.051, 95% CI 1.034-1.067 [p < 0.001] vs HR 1.019, 95% CI 1.007-1.030 [p = 0.001]). Both manual and automatic EOR models showed that patients with gross-total resection have significantly longer overall survival compared with those with subtotal resection (manual vs automatic: HR 1.580, 95% CI 1.291-1.932 [p < 0.001] vs HR 1.395, 95% CI 1.160-1.679 [p < 0.001]), but no significant prognostic difference of gross-total compared with near-total (90%-99%) resection was found. According to the Akaike information criterion and the Bayesian information criterion, all multivariable Cox regression models showed similar goodness-of-fit. Automatically and manually measured EOR and RT volumes have comparable prognostic properties. Automatic segmentation with Raidionics can be used in future studies in patients with glioblastoma.

Can PSMA PET detect intratumour heterogeneity in histological PSMA expression of primary prostate cancer? Analysis of [68Ga]Ga-PSMA-11 and [18F]PSMA-1007.

Prostate-specific membrane-antigen positron emission tomography (PSMA PET) is a promising candidate for non-invasive characterization of prostate cancer (PCa). This study evaluated whether PET with tracers [68Ga]Ga-PSMA-11 or [18F]PSMA-1007 is capable to depict intratumour heterogeneity of histological PSMA expression. Thirty-five patients with biopsy-proven primary PCa without evidence of metastatic disease nor prior interventions were prospectively enrolled. All patients underwent PSMA PET combined with computer tomography (CT) with either [68Ga]Ga-PSMA-11 (cohort I, 20 patients) or [18F]PSMA-1007 (cohort II, 15 patients) followed by radical prostatectomy. Specimens were scanned by ex-vivo CT and histologically prepared. On digitized whole-mount prostate sections, PCa areas with different morphologies were manually defined and H-Score of immunohistochemical PSMA expression was calculated with assistance by artificial intelligence (AI). PCa areas with similar H-Score were unified in segmentation on ex-vivo CT. After co-registration on PSMA PET-CT, Spearman's coefficients of PSMA expression to mean and maximum standardized uptake value (SUVmean and SUVmax) were calculated. Furthermore, the agreement of the co-registered tumour areas to gross tumour volume (GTV) in PSMA PET was analysed. Thirty-two patients were included in the final analysis. For histological PCa areas, immunohistochemical PSMA expression correlated significantly to SUVmean and SUVmax (p < 0.001, p = 0.001). An approximate linear correlation between H-Score and SUVmean / SUVmax was found for tumour areas larger than 400μm² in histology (p < 0.001). Tumour areas with strong PSMA expression showed a significantly larger overlap to GTV in PSMA PET after co-registration than tumour areas with very low PSMA expression (p < 0.01). No significant differences were found between the two tracer cohorts (p = 0.72). PSMA PET with both [68Ga]Ga-PSMA-11 or [18F]PSMA-1007 is able to detect changes in histological PSMA expression within PCa lesions allowing biologically targeted radiotherapy.