rss_2.0Radiology and Oncology FeedSciendo RSS Feed for Radiology and Oncology and Oncology Feed prognostic significance of programmed cell death protein 1 and its ligand on lymphoma cells and tumor-immune cells in diffuse large B-cell lymphoma, not otherwise specified<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Background</title> <p>Diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS) is the most common type non-Hodgkin’s lymphoma, where the treatment of relapsed/refractory cases is the major challenge. Programmed cell death protein 1 (PD-1) and its ligand PD-L1 play a crucial role in the negative regulation of the immune response against the disease. The aim of the study was to analyze the expression of PD-1 and PD-L1 on lymphoma cells (LCs) and tumor-immune cells (TICs) and to investigate their correlation with outcome.</p> </sec> <sec><title style='display:none'>Patients and methods</title> <p>Samples from 283 patients diagnosed with DLBCL, NOS (both germinal center B cell like [GCB] and non-GCB subtypes) were included in the study. Expression of PD-1 and PD-L1 was determined using double immunohistochemical staining (D-IHC) for PD-1/PAX5 and PD-L1/PAX5 on tissue microarrays. LCs were highlighted by D-IHC to obtain more accurate results. Clinical data and histologic diagnoses were obtained from electronic data records. We correlated clinical characteristics, and PD-1 and PD-L1 expression on LCs and TICs with progression-free survival (PFS) and overall survival (OS).</p> </sec> <sec><title style='display:none'>Results</title> <p>Expression of PD-1 on TICs was observed in 38.4% and on LCs in 8.8% of cases, while PD-L1 was expressed on TICs in 46.8% and on LCs in 6.5% of cases. PD-L1 expression on LCs was more frequent in non-GCB subtype (p = 0.047). In addition, patients with PD-L1 expression on LCs had significantly shorter PFS (p = 0.015), and the expression retained significant in the multivariate model (p = 0.034).</p> </sec> <sec><title style='display:none'>Conclusions</title> <p>PD-L1 was more frequently expressed in LCs of the non-GCB subtype. Additionally, PD-L1 in LCs may predict shorter PFS time. D-IHC staining for PD-L1/PAX5 is a feasible method to assess PD-L1 expression on LCs of DLBCL, NOS patients and can be used to identify patients who may benefit from targeted immunotherapy with checkpoint inhibitors.</p> </sec> </abstract>ARTICLEtrue performance and prognostic value of initial bone marrow involvement in diffuse large B-cell lymphoma: a single centre F-FDG PET/CT and bone marrow biopsy evaluation study<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Background</title> <p>Detection of bone marrow involvement (BMI) in diffuse large B-cell lymphoma (DLBCL) typically relies on invasive bone marrow biopsy (BMB) that faces procedure limitations, while <sup>18</sup>F-FDG PET/CT imaging offers a noninvasive alternative. The present study assesses the performance of <sup>18</sup>F-FDG PET/CT in DLBCL BMI detection, its agreement with BMB, and the impact of BMI on survival outcomes.</p> </sec> <sec><title style='display:none'>Patients and methods</title> <p>This retrospective study analyzes baseline <sup>18</sup>F-FDG PET/CT and BMB findings in145 stage II–IV DLBCL patients, evaluating both performance of the two diagnostic procedures and the impact of BMI on survival.</p> </sec> <sec><title style='display:none'>Results</title> <p>DLBCL BMI was detected in 38 patients (26.2%) using PET/CT and in 18 patients (12.4%) using BMB. Concordant results were seen in 79.3% of patients, with 20.7% showing discordant results. Combining PET/CT and BMB data, we identified 29.7% of patients with BMI. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PET/CT for detecting DLBCL BMI were 88.4%, 100%, 100%, 95.3%, and 96.5%, respectively, while BMB showed lower sensitivity (41.9%) and NPV (46.8%). The median overall survival (OS) was not reached in any gender subgroup, with 5-year OS rates of 82% (total), 84% (female), and 80% (male) (p = 0.461), while different International Prognostic Index (IPI) groups exhibited varied 5-year OS rates: 94% for low risk (LR), 91% for low-intermediate risk (LIR), 84% for high-intermediate risk (HIR), and 65% for high risk (HR) (p = 0.0027). Bone marrow involvement did not impact OS significantly (p = 0.979).</p> </sec> <sec><title style='display:none'>Conclusions</title> <p><sup>18</sup>F-FDG PET/CT demonstrated superior diagnostic accuracy compared to BMB. While other studies reported poorer overall and BMI 5-year OS in DLBCL, our findings demonstrated favourable survival data.</p> </sec> </abstract>ARTICLEtrue obesity in cancer<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Background</title> <p>Sarcopenic obesity is a relatively new term. It is a clinical condition characterized by sarcopenia (loss of muscle mass and function) and obesity (increase in fat mass) that mainly affects older adults. As the incidence of sarcopenia and obesity increases worldwide, sarcopenic obesity is becoming a greater problem also in cancer patients. In fact, sarcopenic obesity is associated with poorer treatment outcomes, longer hospital stays, physical disability, and shorter survival in several cancers. Oxidative stress, lipotoxicity, and systemic inflammation, as well as altered expression of skeletal muscle anti-inflammatory myokines in sarcopenic obesity, are also associated with carcinogenesis.</p> </sec> <sec><title style='display:none'>Conclusions</title> <p>Reported prevalence of sarcopenic obesity in cancer varies because of heterogeneity in definitions and variability in diagnostic criteria used to estimate the prevalence of sarcopenia and obesity. Therefore, the aim of this review is to describe the definitions, prevalence, and diagnostic criteria as well as the mechanisms that cancer has in common with sarcopenic obesity.</p> </sec> </abstract>ARTICLEtrue of endoscopic ultrasound-guided fine needle aspiration biopsies in diagnosing pancreatic neoplasms in the paediatric population: experience from a tertiary center and review of the literature<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Background</title> <p>Endoscopic ultrasound-guided fine needle aspiration biopsy (EUS FNAB) is a well established diagnostic method in adult patients, but is rarely used in the paediatric population. The Clinical Department of Gastroenterology at the University Clinical Centre Ljubljana and the Department of Cytopathology at the Institute of Pathology, Faculty of Medicine, University of Ljubljana, Slovenia, have been closely collaborating on EUS FNAB since the introduction in 2010. The aim of the study was to review the cases of EUS FNAB of pancreatic neoplasms in children.</p> </sec> <sec><title style='display:none'>Patients and methods</title> <p>In the digital archive of the Institute of Pathology (IP), Faculty of Medicine (FM), University of Ljubljana (UL), we found 6 cases of EUS FNAB in children, 3 had EUS FNAB of the pancreas, 2 of whom had a cytopathologic diagnosis of a tumour. In the first case, the lesion was ultrasonographically solid, and the cell sample contained branching papillary structures surrounded by aggregates of small cells with nuclear grooves. In the second case, the lesion was ultrasonographically cystic, and predominantly necrosis was seen, with only single preserved cells. Positive nuclear reaction for β-catenin was found in both cases by immunohistochemical staining.</p> </sec> <sec><title style='display:none'>Results</title> <p>In both cases, the cytopathological diagnosis of solid pseudopapillary neoplasm of the pancreas was made, the cases represent the totality of paediatric cases of pancreatic neoplasms from the Children’s Hospital Ljubljana since 2010. There were no adverse events during and after EUS FNAB. A histopathological examination of the tumour resection specimens confirmed the cytopathological diagnosis.</p> </sec> <sec><title style='display:none'>Conclusions</title> <p>Our experience indicates that EUS FNAB is a safe and effective method for diagnosing pancreatic neoplasms in the pediatric population, as supported by the findings in the literature.</p> </sec> </abstract>ARTICLEtrue of diffusion-weighted imaging in response prediction and evaluation after high dose rate brachytherapy in patients with colorectal liver metastases<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Background</title><p>The aim of the study was to assess the role of diffusion-weighted imaging (DWI) to evaluate treatment response in patients with liver metastases of colorectal cancer.</p></sec> <sec><title style='display:none'>Patients and methods</title><p>In this retrospective, observational cohort study, we included 19 patients with 18 responding metastases (R-Mets; follow-up at least one year) and 11 non-responding metastases (NR-Mets; local tumor recurrence within one year) who were treated with high-dose-rate brachytherapy (HDR-BT) and underwent pre- and post-interventional MRI. DWI (qualitatively, mean apparent diffusion coefficient [ADCmean], ADCmin, intraindividual change of ADCmean and ADCmin) were evaluated and compared between pre-interventional MRI, first follow-up after 3 months and second follow-up at the time of the local tumor recurrence (in NR-Mets, mean: 284 ± 122 d) or after 12 months (in R-Mets, mean: 387+/−64 d). Sensitivity, specificity, positive predictive values (PPVs), and negative predictive values (NPVs) for detection of local tumor recurrence were calculated on second follow up, evaluating (1) DWI images only, and (2) DWI with Gd-enhanced T1-weighted images on hepatobiliary phase (contrast-enhanced [CE] T1-weight [T1w] hepatobiliary phase [hb])</p></sec> <sec><title style='display:none'>Results</title><p>ADCmean significantly increased 3 months after HDR-BT in both groups (R-Mets: 1.48 ± 0.44 and NR-Mets: 1.49 ± 0.19 x 10<sup>−3</sup> mm<sup>2</sup>;/s, p &lt; 0.0001 and p = 0.01), however, intraindividual change of ADCmean (175% <italic>vs</italic>.127%, p = 0.03) and ADCmin values (0.44 ± 0.24 to 0.82 ± 0.58 x 10<sup>−3</sup> mm<sup>2</sup>/s) significantly increased only in R-Mets (p &lt; 0.0001 and p &lt; 0.001). ADCmin was significant higher in R-Mets compared to NR-Mets on first follow-up (p = 0.04). Sensitivity (1 <italic>vs</italic>. 0.72), specificity (0.94 <italic>vs</italic>. 0.72), PPV (0.91 <italic>vs</italic>. 0.61) and NPV (1 <italic>vs</italic>. 0.81) could be improved by combining DWI with CE T1w hb compared to DWI only.</p></sec> <sec><title style='display:none'>Conclusions</title><p>DW-MRI seems to be helpful in the qualitative and quantitative evaluation of treatment response after HDR-BT of colorectal metastases in the liver.</p></sec> </abstract>ARTICLEtrue promotes gastric cancer cell migration and angiogenesis via the Wnt/β-catenin pathway<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Background</title> <p>Gastric cancer is an epidemic malignancy that is commonly diagnosed at the late stage. Evidence has elucidated that RAD54B exerts a crucial role in the progress of various tumors, but its specific role and mechanism in gastric cancer remain gloomy.</p> </sec> <sec><title style='display:none'>Materials and methods</title> <p>The level of RAD54B was detected by western blot. RAD54B expression was downregulated or upregulated in both MKN45 and AGS cells by the transfection of shRAD54B or overexpression plasmid, respectively. The role of RAD54B in the growth, migration, invasion and tube formation of gastric cancer was evaluated by Edu, colony formation, transwell and tube formation assays. In addition, the molecular mechanism of RAD54B in gastric cancer was also determined by western blot. Moreover, <italic>in vivo</italic> experiment was conducted in xenografted mice.</p> </sec> <sec><title style='display:none'>Results</title> <p>The expression of RAD54B was discovered to be upregulated in gastric cancer based on the ATGC and GEPIA databases, which was also confirmed in gastric cancer cell lines. Moreover, overexpression of RAD54B enhanced the growth, migration, invasion, tube formation and Wnt/β-catenin signaling axis in AGS and MKN45 cells. As expected, knockdown of RAD54B in AGS and MKN45 cells reversed these promotions. More importantly, <italic>in vivo</italic> assay also verified that RAD54B accelerated the growth of gastric cancer and Wnt/β-catenin signaling pathway.</p> </sec> <sec><title style='display:none'>Conclusions</title> <p>Both loss-of-function and gain-of-function assays demonstrated that RAD54B facilitated gastric cancer cell progress and angiogenesis through the Wnt/β-catenin axis.</p> </sec> </abstract>ARTICLEtrue length and polymorphisms as biomarkers in asbestos-related diseases<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Background</title> <p>Asbestos exposure has been proposed as a risk factor for shorter telomere length. The aim of our study was to investigate whether telomere length in leukocytes and <italic>hTERT</italic> genetic polymorphisms may serve as potential biomarkers for the risk of developing asbestos-related diseases and as biomarkers of progression and chemotherapy response rate in malignant mesothelioma (MM).</p> </sec> <sec><title style='display:none'>Subjects and methods</title> <p>We conducted two retrospective studies. In the first study, a case-control study, telomere length and <italic>hTERT</italic> polymorphisms were determined in patients with MM, subjects with pleural plaques and controls without the asbestos related disease, who were occupationally exposed to asbestos. In the second study, a longitudinal observational study, telomere length was also determined in samples from MM patients before and after chemotherapy. Telomere length was determined by monochromatic multiplex quantitative polymerase chain reaction (PCR), while competitive allele-specific PCR was used to genotype <italic>hTERT</italic> rs10069690, rs2736100 and rs2736098. Logistic regression and survival analysis were used in statistical analysis.</p> </sec> <sec><title style='display:none'>Results</title> <p>Patients with MM had shorter telomere length than subjects with pleural plaques (p &lt; 0.001). After adjustment for age, rs2736098 CT, and rs10069690 TT and CT+TT genotypes were significantly associated with a higher risk of MM (p<sub>adj</sub> = 0.023; p<sub>adj</sub> = 0.026 and p<sub>adj</sub> = 0.017), while rs2736100 AA and CA+AA genotypes conferred to a lower risk for MM compared to all other subjects (p<sub>adj</sub> = 0.017, and p<sub>adj</sub> = 0.026). Telomere length was not associated with a response to chemotherapy (p &gt; 0.05) or time to disease progression (p &gt; 0.05). Carriers of one or two polymorphic rs10069690 T alleles had a good response to chemotherapy (p = 0.039, and p = 0.048), these associations remained statistically significant after adjustment for age (p<sub>adj</sub> = 0.019; p<sub>adj</sub> = 0.017). Carriers of two polymorphic rs2736100 A alleles had a longer time to disease progression (p = 0.038).</p> </sec> <sec><title style='display:none'>Conclusions</title> <p>Shorter telomere length and <italic>hTERT</italic> polymorphisms may serve as a biomarker for the risk of developing MM. Additionally, rs10069690 and rs2736100 polymorphisms, but not telomere length, were associated with a chemotherapy response or MM progression.</p> </sec> </abstract>ARTICLEtrue influence of cytotoxic drugs on the immunophenotype of blast cells in paediatric B precursor acute lymphoblastic leukaemia<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Background</title> <p>Flow cytometry plays is important in the diagnosis of acute lymphoblastic leukaemia (ALL) and when antigen-specific immunotherapy is indicated. We have investigated the effects of prednisolone, vincristine, daunorubicin, asparaginase and methotrexate on the antigen expression on blast cells that could influence the planning of antigen-specific therapy as well as risk-based treatment assignment.</p> </sec> <sec><title style='display:none'>Patients and methods</title> <p>Patients aged ≤ 17 years with <italic>de novo</italic> B-cell ALL (B-ALL) were enrolled in the study. Blast cells were isolated and exposed <italic>in vitro</italic> to 5 individual cytotoxic drugs in logarithmically increasing concentrations. Then, the expression of CD10, CD19, CD20, CD27, CD34, CD45, CD58, CD66c and CD137 antigens was determined by quantitative flow cytometry.</p> </sec> <sec><title style='display:none'>Results</title> <p>Cytotoxic drugs caused dose-dependent or dose-independent modulation of antigen expression. Daunorubicin caused a dose-dependent down-modulation of CD10, CD19, CD34, CD45 and CD58 and an up-modulation of CD137. Vincristine caused a dose-dependent down-modulation of CD19 and CD58 and an up-modulation of CD45. Daunorubicin also caused dose-independent down-modulation of CD27 and prednisolone down-modulation of CD10, CD19, CD27, CD34 and CD58. Down-modulation of CD20 was detected only in relation to the specific dose of daunorubicin.</p> </sec> <sec><title style='display:none'>Conclusions</title> <p>The results of the study have shown that cytotoxic drugs can alter the expression of antigens that are important for immunotherapy. Importantly, daunorubicin, prednisolone and vincristine caused down-modulation of CD19 and CD58, suggesting that these drugs are better avoided during bridging therapy prior to bispecific antibodies or CAR-T cell therapy. In addition, immunophenotypic changes on blast cells induced by different drugs could also influence risk-based treatment assignment.</p> </sec> </abstract>ARTICLEtrue of nutritional status and body composition on postoperative events and outcome in patients treated for primary localized retroperitoneal sarcoma<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Background</title><p>Retroperitoneal sarcomas (RPS) are rare tumours of mesenchymal origin, commonly presented as a large tumour mass at time of diagnosis. We investigated the impact of body composition on outcome in patients operated on for primary localized RPS.</p></sec> <sec><title style='display:none'>Patients and methods</title><p>We retrospectively analysed data for all patients operated on for primary RPS at our institution between 1999 and 2020. Preoperative skeletal muscle area (SMA), visceral and subcutaneous adipose tissue area (VAT and SAT) and muscle radiation attenuation (MRA) were calculated using computed tomography scans at the level of third lumbar vertebra. European Working Group on Sarcopenia in Older People (EWGSOP2) criteria were applied to define myopenia. Using maximum log-rank statistic method we determined the optimal cut-off values of body composition parameters. Myosteatosis was defined based on determined MRA cut-offs.</p></sec> <sec><title style='display:none'>Results</title><p>In total 58 patient were eligible for the study. With a median follow-up of 116 months, the estimated 5-year overall survival (OS) and local-recurrence free survival (LRFS) were 66.8% and 77.6%, respectively. Patients with myopenia had significantly lower 5-year OS compared to non-myopenic (p = 0.009). Skeletal muscle index and subcutaneous adipose tissue index predicted LRFS on univariate analysis (p = 0.052 and p = 0.039, respectively). In multivariate analysis high visceral-to-subcutaneous adipose tissue area ratio (VSR) independently predicted higher postoperative complication rate (89.2% <italic>vs</italic>. 10.8%, p = 0.008). Myosteatosis was associated with higher postoperative morbidity.</p></sec> <sec><title style='display:none'>Conclusions</title><p>Myopenia affected survival, but not postoperative outcome in RPS. Visceral obesity, VSR (&gt; 0.26) and myosteatosis were associated with higher postoperative morbidity. VSR was better prognostic factor than VAT in RPS.</p></sec> </abstract>ARTICLEtrue influence of anaesthesia on cancer growth<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Background</title> <p>Oncological patients make up a large proportion of all surgical patients. Through its influence on the patient’s inflammatory and immune system, the choice of anaesthetic technique has an indirect impact on the health of the individual patient and on public health. Both the specific and the non-specific immune system have a major influence on the recurrence of carcinomas. The pathophysiological basis for growth and metastasis after surgery is the physiological response to stress. Inflammation is the organism’s universal response to stress. Anaesthetics and adjuvants influence perioperative inflammation in different ways and have an indirect effect on tumour growth and metastasis. <italic>In vitro</italic> studies have shown how individual anaesthetics influence the growth and spread of cancer, but clinical studies have not confirmed these results. Nevertheless, it is advisable to use an anaesthetic that has shown lesser effect on the growth of cancer cells <italic>in vitro</italic>.</p> </sec> <sec><title style='display:none'>Conclusions</title> <p>In this review, we focus on the area of the effects of anaesthesia on tumour growth. The field is still relatively unexplored, there are only few clinical prospective studies and their results are controversial. Based on the review of new research findings we report on recommendations about anaesthetics and anaesthetic techniques that might be preferable for oncological surgical procedures.</p> </sec> </abstract>ARTICLEtrue through the imaging perspective: the importance of imaging necrosis in glioma diagnosis and prognostic prediction – single centre experience<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Background</title><p>The aim of the study was to investigate the diagnostic value of imaging necrosis (Im<sub>necrosis</sub>) in grading, predict the genotype and prognosis of gliomas, and further assess tumor necrosis by dynamic contrast-enhanced MR perfusion imaging (DCE-MRI).</p></sec> <sec><title style='display:none'>Patients and methods</title><p>We retrospectively included 150 patients (104 males, mean age: 46 years old) pathologically proved as adult diffuse gliomas and all diagnosis was based on the 2021 WHO central nervous system (CNS) classification. The pathological necrosis (Pa<sub>necrosis</sub>) and gene mutation information were collected. All patients underwent conventional and DCE-MRI examinations and had been followed until May 31, 2021. The Im<sub>necrosis</sub> was determined by two experienced neuroradiologists. DCE-MRI derived metric maps have been post-processed, and the mean value of each metric in the tumor parenchyma, peritumoral and contralateral area were recorded.</p></sec> <sec><title style='display:none'>Results</title><p>There was a strong degree of inter-observer agreement in defining Im<sub>necrosis</sub> (Kappa = 0.668, p &lt; 0.001) and a strong degree of agreement between Im<sub>necrosis</sub> and Pa<sub>necrosis</sub> (Kappa = 0.767, p &lt; 0.001). Compared to low-grade gliomas, high-grade gliomas had more Im<sub>necrosis</sub> (85.37%, p &lt; 0.001), and Im<sub>necrosis</sub> significantly increased with the grade of gliomas increasing. And Im<sub>necrosis</sub> was significantly more identified in <italic>IDH</italic>-wildtype, <italic>1p19q</italic>-non-codeletion, and <italic>CDKN2A/B</italic>-homozygous-deletion gliomas. Using multivariate Cox regression analysis, Im<sub>necrosis</sub> was an independent and unfavorable prognosis factor (Hazard Ratio = 2.113, p = 0.046) in gliomas. Additionally, extravascular extracellular volume fraction (<italic>ve</italic>) in tumor parenchyma derived from DCE-MRI demonstrated the highest diagnostic efficiency in identifying Pa<sub>necrosis</sub> and Im<sub>necrosis</sub> with high specificity (83.3% and 91.9%, respectively).</p></sec> <sec><title style='display:none'>Conclusions</title><p>Im<sub>necrosis</sub> can provide supplementary evidence beyond Pa<sub>necrosis</sub> in grading, predicting the genotype and prognosis of gliomas, and <italic>ve</italic> in tumor parenchyma can help to predict tumor necrosis with high specificity.</p></sec> </abstract>ARTICLEtrue equivalence of different types of electric pulses for electrochemotherapy with cisplatin − an study<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Background</title> <p>Electrochemotherapy (ECT) is a treatment involving the administration of chemotherapeutics drugs followed by the application of 8 square monopolar pulses of 100 μs duration at a repetition frequency of 1 Hz or 5000 Hz. However, there is increasing interest in using alternative types of pulses for ECT. The use of high-frequency short bipolar pulses has been shown to mitigate pain and muscle contractions. Conversely, the use of millisecond pulses is interesting when combining ECT with gene electrotransfer for the uptake of DNA-encoding proteins that stimulate the immune response with the aim of converting ECT from a local to systemic treatment. Therefore, the aim of this study was to investigate how alternative types of pulses affect the efficiency of the ECT.</p> </sec> <sec><title style='display:none'>Materials and methods</title> <p>We performed <italic>in vitro</italic> experiments, exposing Chinese hamster ovary (CHO) cells to conventional ECT pulses, high-frequency bipolar pulses, and millisecond pulses in the presence of different concentrations of cisplatin. We determined cisplatin uptake by inductively coupled plasma mass spectrometry and cisplatin cytotoxicity by the clonogenic assay.</p> </sec> <sec><title style='display:none'>Results</title> <p>We observed that the three tested types of pulses potentiate the uptake and cytotoxicity of cisplatin in an equivalent manner, provided that the electric field is properly adjusted for each pulse type. Furthermore, we quantified that the number of cisplatin molecules, resulting in the eradication of most cells, was 2−7 × 10<sup>7</sup> per cell.</p> </sec> <sec><title style='display:none'>Conclusions</title> <p>High-frequency bipolar pulses and millisecond pulses can potentially be used in ECT to reduce pain and muscle contraction and increase the effect of the immune response in combination with gene electrotransfer, respectively.</p> </sec> </abstract>ARTICLEtrue study of ‘Sandwich treatment’ for motor area large brain metastases (LBM) with diameter over 3 cm<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Background</title> <p>The objective of the present study was to explore the effectiveness and safety of ‘Sandwich treatment’ strategy for large brain metastases (LBM) with diameter over 3 cm (minimum volume &gt;= 15 cm<sup>3</sup>) located in motor area.</p> </sec> <sec><title style='display:none'>Patients and methods</title> <p>Patients from four gamma knife center that received ‘Sandwich treatment’ were retrospectively studied from January 2016 to March 2023. The strategy was one-week treatment course including 2 stages of stereotactic radiosurgery (SRS) and using bevacizumab once during SRS gap. The tumor volume and peri-tumor edema changes were analyzed before and after ‘Sandwich treatment’. Manual muscle testing (MMT) score and Barthel Index (BI) score were used to evaluate the changes of patients’ movement and physical strength rehabilitation. The patients’ overall survival (OS) and tumor local control (TLC) rate was calculated. Cox regression model was used to analyze the risk factors that related to TLC.</p> </sec> <sec><title style='display:none'>Results</title> <p>61 patients with 72 lesions received the ‘Sandwich treatment’. The median prescription dose was 13.0 Gy and 12.5 Gy at the first- and second-stage SRS. The mean tumor volume at the time of ‘Sandwich treatment’ and 3 months later was 20.1 cm<sup>3</sup> and 12.3, respectively (P &lt; 0.01). The mean peri-tumor edema volume at the first- and second-stage SRS was 12.6 cm<sup>3</sup> and 5.2 cm<sup>3</sup>, respectively (P &lt; 0.01). Patients’ median MMT score improved from 6 at the beginning to 8 at the end of ‘Sandwich treatment’ (P &lt; 0.01), BI score was also greatly improved from 45 at the time of ‘Sandwich treatment’ to 95 after 3 months (P &lt; 0.01). Patients’ median OS was 14.0 months, and the 3, 6, 12 months OS rate was 92.0%, 86.0% and 66.0%, respectively. The TLC rate at 3, 6, 12 months was 98.4%, 93.4%, and 85.3%, respectively. Patients with lung cancer had lower risk of tumor relapse. The cumulative incidence of patient’s hemorrhage and radiation necrosis was 4.92% (3/61) and 13.11% (8/61) after ‘Sandwich treatment’.</p> </sec> <sec><title style='display:none'>Conclusions</title> <p>‘Sandwich treatment’ strategy is safe and effective for LBM located in motor area. The strategy could rapidly improve the patients’ movement and enhance their physical strength rehabilitation.</p> </sec> </abstract>ARTICLEtrue retrospective study on improving the accuracy of radiotherapy for patients with breast cancer with lymph node metastasis using Styrofoam<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Background</title> <p>To retrospectively analyze the accuracy of radiotherapy using cone beam computed tomography (CBCT), Styrofoam fixation, and breast bracket fixation in the chest wall target area and supraclavicular lymphatic drainage area (supraclavicular target area) of patients with breast cancer.and compare the setting efficiency and comfort satisfaction.</p> </sec> <sec><title style='display:none'>Patients and methods</title> <p>A total of 65 patients with postoperative lymphatic metastasis of breast cancer, including 36 cases of Styrofoam fixation and 29 cases of breast bracket fixation, were recruited from March 2021 to August 2022 and retrospectively analyzed. All the patients underwent CBCT scans weekly, and the setup errors of the chest wall and supraclavicular target volume were compared and recorded. The planning target volume (PTV) margins of the two groups were calculated using the correlation M<sub>PTV</sub> = 2.5Σ + 0.7σ. The setup time and comfort satisfaction scores of the two groups were recorded and analyzed. The correlations among errors in each direction were analyzed using the Pearson correlation analysis.</p> </sec> <sec><title style='display:none'>Results</title> <p>There was a significant difference in the left-right direction (X) axis of the chest wall target area between the Styrofoam and breast bracket groups (1.59 ± 1.47 mm <italic>vs.</italic> 2.05 ± 1.64 mm, P = 0.012). There were statistical differences in the ventrodorsal direction (Z) and bed angle of the supraclavicular target area, the data were (1.36 ± 1.27 mm <italic>vs.</italic> 1.75 ± 1.55 mm, P = 0.046; 0.47 ± 0.47° <italic>vs.</italic> 0.66 ± 0.59°, P = 0.006, respectively). In the X, Y, and Z directions, the respective PTV margins of the two groups in the chest wall target area were 5.01 mm, 5.99 mm, and 5.47 mm in the Styrofoam group, while those in the breast bracket group were 6.10 mm, 6.34 mm, and 6.10 mm, respectively. Moreover, the PTV margins of the supraclavicular target in the three directions were 3.69 mm, 3.86 mm, and 4.28 mm in the Styrofoam group, while those in the breast bracket group were 3.99 mm, 3.72 mm, and 5.45 mm, respectively. The setup time of the two groups was 3.4 ± 1.1 min and 5.5 ± 3.1 min (P = 0.007). The subjective comfort satisfaction scores of the two groups were 27.50 ± 1.24 and 25.44 ± 1.23 (P &lt; 0.001).</p> </sec> <sec><title style='display:none'>Conclusions</title> <p>The application of Styrofoam fixation in radiotherapy of breast cancer in the supraclavicular lymph node area has several advantages as compared to breast bracket fixation, including higher positioning accuracy, smaller external expansion boundary, improved work efficiency, and patients’ comfort, which might provide a reference for clinical work.</p> </sec> </abstract>ARTICLEtrue assessment of bone marrow infiltration and characterization of tumor burden using dual-layer spectral CT in patients with multiple myeloma<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Background</title> <p>The aim of the study was to evaluate whether virtual calcium subtraction (VNCa) image extracted from dual-layer spectral CT could estimate bone marrow (BM) infiltration with MRI as the reference standard and characterize tumor burden in patients with multiple myeloma (MM).</p> </sec> <sec><title style='display:none'>Patients and methods</title> <p>Forty-seven patients with newly diagnosed MM were retrospectively enrolled. They had undergone whole-body low-dose dual-layer spectral CT (DLCT) and whole-body MRI within one week. VNCa images with calcium-suppressed (CaSupp) indices ranging from 25 to 95 at an interval of 10 and apparent diffusion coefficient (ADC) maps were quantitatively analyzed on vertebral bodies L1−L5 at the central slice of images. The optimal combination was selected by correlation analysis between CT numbers and ADC values. Then, it was used to characterize tumor burden by correlation analysis and receiver operating characteristic (ROC) curves analysis, including plasma cell infiltration rate (PCIR), high serum-free light chains (SFLC) ratio and the high-risk cytogenetic (HRC) status.</p> </sec> <sec><title style='display:none'>Results</title> <p>The most significant quantitative correlation between CT numbers of VNCa images and ADC values could be found at CaSupp index 85 for averaged L1−L5 (r = 0.612, p &lt; 0.001). It allowed quantitative evaluation of PCIR (r = 0.835, p &lt; 0.001). It could also anticipate high SFLC ratio and the HRC status with <italic>area under the curve</italic> (<italic>AUC</italic>) of 0.876 and 0.760, respectively.</p> </sec> <sec><title style='display:none'>Conclusions</title> <p>The VNCa measurements of averaged L1−L5 showed the highest correlation with ADC at CaSupp index 85. It could therefore be used as additional imaging biomarker for non-invasive assessment of tumor burden if ADC is not feasible.</p> </sec> </abstract>ARTICLEtrue diffusion coefficient measurements of bone marrow infiltration patterns in multiple myeloma for the assessment of tumor burden – a feasibility study<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Background</title> <p>The purpose of our study was to explore and compare the tumor burden of different bone marrow infiltration patterns and evaluate the feasibility of apparent diffusion coefficient (ADC) value to identify patterns in multiple myeloma (MM).</p> </sec> <sec><title style='display:none'>Patients and methods</title> <p>Ninety-three patients with newly diagnosed multiple myeloma and 23 controls had undergone routine magnetic resonance imaging (MRI) and diffusion-weighted MRI (DWI) from January 2019 to November 2020. Five bone marrow (BM) infiltration patterns were allocated according to routine MRI. The laboratory data and ADC values of patterns were analyzed and compared. ROC analysis was used to establish the best diagnostic ADC threshold value for identifying these patterns and distinguishing normal pattern from controls. Besides, the correlation between the ADC values of diffuse pattern and the plasma cells ratio was assessed.</p> </sec> <sec><title style='display:none'>Results</title> <p>The values of hemoglobin, beta-2 microglobulin (β2-MG), plasma cell, M protein, the percentages of stage, high-risk fluorescence in situ hybridization, and ADC values showed significant difference among patterns. ADC<sub>mean</sub> at a specific value (368.5×10<sup>−6</sup> mm<sup>2</sup>/s) yielded a maximum specificity (95.5%) and sensitivity (92.0%) in diagnosing MM. A specific value (335.5×10<sup>−6</sup>mm<sup>2</sup>/s) yielded a maximum specificity (84.7%) and sensitivity (88.0%) in discriminating visually normal pattern in MM from controls. There was a moderate positive correlation between the plasma cells ratio and ADCs of diffuse infiltration patterns (r = 0.648, P &lt; 0.001).</p> </sec> <sec><title style='display:none'>Conclusions</title> <p>The bone marrow infiltration patterns in MM patients can indicate the tumor burden and ADC value has the ability to discriminate these patterns objectively.</p> </sec> </abstract>ARTICLEtrue of short-term effect of platelet-rich plasma treatment of tendinosis using texture analysis of ultrasound images<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Background</title> <p>Computer-aided diagnosis (<italic>i.e.</italic>, texture analyses) tools are becoming increasingly beneficial methods to monitor subtle tissue changes. The aim of this pilot study was to investigate short-term effect of platelet rich plasma (PRP) treatment in supraspinatus and common extensor of the forearm tendinosis by using texture analysis of ultrasound (US) images as well as by clinical questionnaires.</p> </sec> <sec><title style='display:none'>Patients and methods</title> <p>Thirteen patients (7 male and 6 female, age 36–60 years, mean age 51.2 ± 5.2) were followed after US guided PRP treatment for tendinosis of two tendons (9 patients with lateral epicondylitis and 4 with supraspinatus tendinosis). Clinical and US assessment was performed prior to as well as 3 months after PRP treatment with validated clinical questionnaires. Tissue response in tendons was assessed by using gray level run length matrix method (GLRLM) of US images.</p> </sec> <sec><title style='display:none'>Results</title> <p>All patients improved of tendinosis symptoms after PRP treatment according to clinical questionnaires. Almost all GLRLM features were statistically improved 3 months after PRP treatment. GLRLM-long run high gray level emphasis (LRLGLE) revealed the best moderate positive and statistically significant correlation after PRP (<italic>r</italic> = 0.4373, <italic>p</italic> = 0.0255), followed by GLRLM-low gray level run emphasis (LGLRE) (<italic>r</italic> = 0.3877, <italic>p</italic> = 0.05).</p> </sec> <sec><title style='display:none'>Conclusions</title> <p>Texture analysis of tendinosis US images was a useful quantitative method for the assessment of tendon remodeling after minimally invasive PRP treatment. GLRLM features have the potential to become useful imaging biomarkers to monitor spatial and time limited tissue response after PRP, however larger studies with similar protocols are needed.</p> </sec> </abstract>ARTICLEtrue SSTR-PET/CT for predicting response and survival outcomes in patients with pancreatic neuroendocrine tumors receiving CAPTEM<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Background</title> <p>This study aimed to evaluate the predictive and monitoring role of somatostatin receptor (SSTR) positron emission tomography-computed tomography (PET/CT) and clinical parameters in patients with neuroendocrine liver metastases (NELM) from pancreatic neuroendocrine tumors (pNET) receiving capecitabine and temozolomide (CAPTEM).</p> </sec> <sec><title style='display:none'>Patients and methods</title> <p>This retrospective study included twenty-two patients with pNET and NELM receiving CAPTEM who underwent pre- and post-therapeutic <sup>68</sup>Ga-DOTATATE/-TOC PET/CT. Imaging (including standardized uptake value [SUV] of target lesions [NELM and pNET], normal spleen and liver) and clinical (Chromogranin A [CgA], Ki-67) parameters were assessed. Treatment outcome was evaluated as response according to RECIST 1.1, progression free survival (PFS) and overall survival (OS).</p> </sec> <sec><title style='display:none'>Results</title> <p>The median PFS (mPFS) was 7 months. Responders had a significantly longer mPFS compared to non-responders (10 <italic>vs</italic>. 4 months p = 0.022). Median OS (mOS) was 33 months (mOS: responders = 80 months, non-responders = 24 months p = 0.182). Baseline imaging showed higher SUV in responders, including absolute SUV, tumor-to-spleen (T/S), and tumor-to-liver (T/L) ratios (p &lt; 0.02). All SUV parameters changed only in the responders during follow-up. Univariable Cox regression analysis identified baseline Tmax/Smean ratio and percentage change in size of pNETs as significant factors associated with PFS. A baseline Tmax/Smean ratio &lt; 1.5 was associated with a shorter mPFS (10 <italic>vs</italic>. 4 months, (p &lt; 0.05)). Prognostic factors for OS included age, percentage change in CgA and in T/S ratios in univariable Cox regression.</p> </sec> <sec><title style='display:none'>Conclusions</title> <p>SSTR-PET/CT can be useful for predicting response and survival outcomes in pNET patients receiving CAPTEM: Higher baseline SUV values, particularly Tmax/Smean ratios of liver metastases were associated with better response and prolonged PFS.</p> </sec> </abstract>ARTICLEtrue of tumor volume changes during preoperative radiotherapy for extremity soft tissue sarcoma: a new strategy of adaptive radiotherapy<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Background</title> <p>Using adaptive radiotherapy (ART), to determine objective clinical criteria that identify extremity soft tissue sarcoma (ESTS) patients requiring adaptation of their preoperative radiotherapy (RT) plan.</p> </sec> <sec><title style='display:none'>Patients and methods</title> <p>We included 17 patients with a lower extremity ESTS treated between 2019 and 2021 with preoperative RT, using helicoidal intensity-modulated RT (IMRT) tomotherapy, before surgical resection. We collected clinical, tumor parameters and treatment data. Repositioning was ascertained by daily Megavoltage computed tomography (MVCT) imaging. Using the PreciseART technology we retrospectively manually delineated at least one MVCT for each patient per week and recorded volume and dosimetric parameters. A greater than 5% change between target volume and planned target volume (PTV) dosimetric coverage from the initial planning CT scan to at least one MVCT was defined as clinically significant.</p> </sec> <sec><title style='display:none'>Results</title> <p>All 17 patients experienced significant tumor volume changes during treatment; 7 tumors grew (41%) and 10 shrank (59%). Three patients (18%), all undifferentiated pleomorphic sarcomas (UPS) with increased volume changes, experienced significant reductions in tumor dose coverage. Seven patients required a plan adaptation, as determined by practical criteria applied in our departmental practice. Among these patients, only one ultimately experienced a significant change in PTV coverage. Three patients had a PTV decrease of coverage. Among them, 2 did not receive plan adaptation according our criteria. None of the patients with decreased tumor volumes had reduced target volume coverage. Monitoring volume variations by estimating gross tumor volume (GTV) on MVCT, in addition to axial and sagittal linear tumor dimensions, appeared to be most effective for detecting reductions in PTV coverage throughout treatment.</p> </sec> <sec><title style='display:none'>Conclusions</title> <p>Variations in ESTS volume are evident during preoperative RT, but significant dosimetric variations are rare. Specific attention should be paid to grade 2–3 UPSs during the first 2 weeks of treatment. In the absence of dedicated software in routine clinical practice, monitoring of tumor volume changes by estimating GTV may represent a useful strategy for identifying patients whose treatment needs to be replanned.</p> </sec> </abstract>ARTICLEtrue prognostic significance of tumor-immune microenvironment in ascites of patients with high-grade serous carcinoma<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Background</title> <p>High-grade serous carcinoma (HGSC) is often associated with ascites at presentation. Our objective was to quantify immune cells (ICs) in ascites prior to any treatment was given and evaluate their impact on progression-free survival (PFS) and overall survival (OS).</p> </sec> <sec><title style='display:none'>Patients and methods</title> <p>Forty-seven patients with primary HGSC and ascites were included. Flow-cytometric analysis was performed to detect percentages of CD3<sup>+</sup> T cells (CD4<sup>+</sup>, CD8<sup>+</sup>, Tregs, and NKT cells), B cells, NK cells (CD56<sup>bright</sup>CD16<sup>−</sup> and CD56<sup>dim</sup>CD16<sup>+</sup> subsets), macrophages and dendritic cells (DCs). Furthermore, CD103 expression was analyzed on T cells and their subsets, while PD-1 and PD-L1 expression on all ICs. Cut-off of low and high percentages of ICs was determined by the median of variables, and correlation with PFS and OS was calculated.</p> </sec> <sec><title style='display:none'>Results</title> <p>CD3<sup>+</sup> cells were the predominant ICs (median 51%), while the presence of other ICs was much lower (median ≤10%). CD103<sup>+</sup> expression was mostly present on CD8<sup>+</sup>, and not CD4<sup>+</sup> cells. PD-1 was mainly expressed on CD3<sup>+</sup> T cells (median 20%), lower expression was observed on other ICs (median ≤10%). PD-L1 expression was not detected. High percentages of CD103<sup>+</sup>CD3<sup>+</sup> T cells, PD-1<sup>+</sup> Tregs, CD56<sup>bright</sup>CD16<sup>−</sup> NK cells, and DCs correlated with prolonged PFS and OS, while high percentages of CD8<sup>+</sup> cells, macrophages, and PD-1<sup>+</sup>CD56<sup>bright</sup>CD16<sup>−</sup> NK cells, along with low percentages of CD4<sup>+</sup> cells, correlated with better OS only. DCs were the only independent prognostic marker among all ICs.</p> </sec> <sec><title style='display:none'>Conclusions</title> <p>Our results highlight the potential of ascites tumor-immune microenvironment to provide additional prognostic information for HGSC patients. However, a larger patient cohort and longer follow-up are needed to confirm our findings.</p> </sec> </abstract>ARTICLEtrue