The prognostic effect of mechanical, ultrastructural, and ECM signatures in glioblastoma core and rim.

Glioblastoma (GBM) is a highly invasive, aggressive brain cancer that carries a median survival of 15 months and is resistant to standard therapeutics. Recent studies have demonstrated that intratumoral heterogeneity plays a critical role in promoting resistance by mediating tumor adaptation through microenvironmental cues. GBM can be separated into two distinct regions-a core and a rim, which are thought to drive specific aspects of tumor evolution. These differences in tumor progression are regulated by the diverse biomolecular and biophysical signals in these regions, but the acellular biophysical characteristics remain poorly described. This study investigates the mechanical and ultrastructural characteristics of the tumor extracellular matrix (ECM) in patient-matched GBM core and rim tissues. Seven patient-matched tumor core and rim samples and one non-neoplastic control were analyzed using atomic force microscopy, scanning electron microscopy, and immunofluorescence imaging to quantify mechanical, ultrastructural, and ECM composition changes. The results reveal significant differences in biophysical parameters between GBM core, rim, and non-neoplastic tissues. The GBM core is stiffer, denser, and is rich in ECM proteins hyaluronic acid and tenascin-C when compared to tumor rim and non-neoplastic tissues. These alterations are intimately related and have prognostic effect with stiff, dense tissue correlating with longer progression-free survival. These findings reveal new insights into the spatial heterogeneity of biophysical parameters in the GBM tumor microenvironment and identify a set of characteristics that may correlate with patient prognosis. In the long term, these characteristics may aid in the development of strategies to combat therapeutic resistance.

Niraparib Population Pharmacokinetics and Exposure-Response Relationships in Patients With Newly Diagnosed Advanced Ovarian Cancer.

PURPOSE: Niraparib is a poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitor approved for the maintenance treatment of advanced ovarian cancer (OC). Niraparib was originally approved in recurrent OC at a fixed starting dose (FSD) of 300 mg once daily (QD). This analysis characterized the population pharmacokinetics (PK) of niraparib and evaluated the relationships between exposure, efficacy, and safety to support clinical use of an individualized dosing strategy, in which the starting dose of niraparib was adjusted based on patient characteristics to improve the benefit-risk profile. METHODS: A population PK model was developed by pooling data from four niraparib clinical trials (PN001 [n = 104], QUADRA [n = 455], NOVA [n = 403], and PRIMA [n = 480]) in patients with solid tumors, including OC. Exposure-response analyses were conducted to explore the relationships of niraparib exposure with progression-free survival (PFS) and adverse events in the PRIMA study. A multivariate logistic regression model was also developed to estimate the probability of grade ≥3 thrombocytopenia, using data from patients enrolled in PRIMA and NOVA. The impact of an individualized starting dose (ISD) regimen (200 mg QD in patients with body weight [BW] <77 kg or platelet count [PLT] <150,000/µL, or 300 mg QD in patients with BW ≥77 kg and PLT ≥150,000/µL) on systemic exposure, efficacy, and safety was assessed. FINDINGS: Niraparib disposition was best described by a 3-compartment model with linear elimination. Key covariates included baseline creatinine clearance, BW, albumin, and age, all of which had minor effects on niraparib exposure. Comparable model-predicted exposure up to the time of disease progression/death or censoring in the 300-mg FSD and 200-/300-mg ISD groups was consistent with the lower rate of dose reduction in the ISD groups. No consistent niraparib exposure-response relationship was observed for efficacy in all PRIMA patients (first-line OC), and no statistically significant difference was seen in PFS curves for patients receiving a niraparib dose of 200 mg versus 300 mg. In the multivariate regression model, performed using combined data from PRIMA and NOVA, higher niraparib exposure (area under the concentration-time curve at steady-state [AUCss]), lower BW, and lower PLT were associated with an increased risk of grade ≥3 thrombocytopenia. IMPLICATIONS: Population PK and exposure-response analyses support use of an ISD to improve the safety profile of niraparib, including reducing the rate of grade ≥3 thrombocytopenia, without compromising efficacy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01847274 (NOVA), NCT00749502 (PN001), NCT02655016 (PRIMA), NCT02354586 (QUADRA), www. CLINICALTRIALS: gov.

Predictors of long-term progression-free survival in patients with ovarian cancer treated with niraparib in the PRIMA/ENGOT-OV26/GOG-3012 study.

OBJECTIVE: To identify characteristics associated with long-term progression-free survival (≥2 years) in patients with advanced ovarian cancer treated with niraparib first-line maintenance therapy in the phase III PRIMA/ENGOT-OV26/GOG-3012 study. METHODS: In this post hoc analysis of PRIMA, patients randomized to niraparib were grouped based on investigator-assessed progression-free survival (progressive disease/censoring <2 years or ≥2 years after randomization). Variables assessed for predictive value were Eastern Cooperative Oncology Group performance status, International Federation of Gynecology and Obstetrics (FIGO) stage at diagnosis, clinical response to platinum-based chemotherapy, number of prior chemotherapy cycles, primary tumor location, body mass index, categorical age, debulking surgery type, number of baseline target lesions, number of baseline non-target lesions, BRCA/homologous recombination-deficiency status, residual disease status, and duration from end of chemotherapy to randomization. Logistic regression modeling using backward elimination (significance level=0.15) identified covariates associated with long-term progression-free survival (clinical cut-off date November 17, 2021). RESULTS: Of 487 patients randomized to niraparib, 152 (31%) had progressive disease/censoring ≥2 years after randomization. Multivariable logistic regression modeling using backward elimination identified BRCA1/2 mutation/homologous recombination deficiency status (p<0.0001), FIGO stage (p=0.041), primary tumor location (p=0.095), and number of baseline non-target lesions (p=0.0001) to be associated with long-term progression-free survival. Patients significantly more likely to achieve progression-free survival of ≥2 years in the final model were those with BRCA1- and BRCA2-mutated/homologous recombination-deficient tumors or BRCA wild-type/not determined/homologous recombination-deficient tumors (vs BRCA wild-type/homologous recombination-proficient/not determined tumors), FIGO stage III (vs IV), and 0 or 1 baseline non-target lesions (vs ≥2 baseline non-target lesions). CONCLUSIONS: The hypothesis-generating results of this analysis suggest that BRCA1/2 mutation/homologous recombination-deficiency status, FIGO stage, and number of baseline non-target lesions may predict progression-free survival of ≥2 years in patients with advanced ovarian cancer receiving niraparib first-line maintenance therapy. TRIAL REGISTRATION NUMBER: NCT02655016.

Intramedullary Threaded Nail Fixation of Distal Ulnar Fractures: The Surgical Technique and Case Series.

BACKGROUND:  To describe the surgical technique of non-compressive intramedullary threaded nail (IMTN) fixation of distal ulnar neck fractures and present the clinical and radiographic outcomes of four patients treated with this novel technique. METHODS: At a single Level 1 Trauma Center, a retrospective review was conducted for patients with distal ulnar neck fractures treated with retrograde IMTN between 2022 and 2024. Exclusion criteria included inadequate follow-up. A single surgeon performed all procedures using percutaneous retrograde IMTN fixation through the central disc of the triangular fibrocartilage complex (TFCC). Patients initiated a range of motion (ROM) protocol two weeks post-operatively. Post-operative radiographic images were used to calculate the ratio of IMTN diameter to the distal ulnar medullary isthmus diameter proximal to the fracture site. Radiographic changes in displacement, angulation, and ulnar variance were calculated between the first and last follow-up radiographs. Functional outcomes including grip strength and ROM were collected. RESULTS: Four patients with distal ulnar neck fractures were treated with retrograde IMTN between 2022 and 2024. They were followed for a minimum of three months post-operatively. All were female with an average age of 65 years. All distal ulna fractures were associated with operatively treated intraarticular distal radius fractures. All patients were treated with 75 mm length and 4.5 mm diameter IMTNs. IMTN-to-Isthmus ratio was greater than 60% in all cases. Average radiographic displacement and angulation were unchanged at the final follow-up. The average ulnar variance increased by 1.2 mm. At the final follow-up, there were no post-operative complications. No cases demonstrated ulnar-sided wrist pain, nonunion, or required revision surgery. CONCLUSIONS: Retrograde IMTN fixation is a novel surgical technique for the treatment of distal ulnar neck fractures. We found limited but promising post-operative radiographic and functional outcomes in our patients without reported ulnar-sided wrist pain, nonunion, or need for hardware removal.

Targeted mapping and utilization of the perihepatic surface for therapeutic beta cell replacement and retrieval in diabetic non-human primates.

Introduction: Successful diabetes reversal using pancreatic islet transplantation by various groups illustrates the significant achievements made in cell-based diabetes therapy. While clinically, intraportal islet delivery is almost exclusively used, it is not without obstacles, including instant blood-mediated inflammatory reaction (IBMIR), relative hypoxia, and loss of function over time, therefore hindering long-term success. Here we demonstrate the perihepatic surface of non-human primates (NHPs) as a potential islet delivery site maximizing favorable characteristics, including proximity to a dense vascular network for adequate oxygenation while avoiding IBMIR exposure, maintenance of portal insulin delivery, and relative ease of accessibility through minimally invasive surgery or percutaneous means. In addition, we demonstrate a targeted mapping technique of the perihepatic surface, allowing for the testing of multiple experimental conditions, including a semi-synthetic hydrogel as a possible three-dimensional framework to improve islet viability. Methods: Perihepatic allo-islet cell transplants were performed in immunosuppressed cynomolgus macaques using a targeted mapping technique to test multiple conditions for biocompatibility. Transplant conditions included islets or carriers (including hydrogel, autologous plasma, and media) alone or in various combinations. Necropsy was performed at day 30, and histopathology was performed to assess biocompatibility, immune response, and islet viability. Subsequently, single-injection perihepatic allo-islet transplant was performed in immunosuppressed diabetic cynomolgus macaques. Metabolic assessments were measured frequently (i.e., blood glucose, insulin, C-peptide) until final graft retrieval for histopathology. Results: Targeted mapping biocompatibility studies demonstrated mild inflammatory changes with islet-plasma constructs; however, significant inflammatory cell infiltration and fibrosis were seen surrounding sites with the hydrogel carrier affecting islet viability. In diabetic NHPs, perihepatic islet transplant using an autologous plasma carrier demonstrated prolonged function up to 6 months with improvements in blood glucose, exogenous insulin requirements, and HbA1c. Histopathology of these islets was associated with mild peri-islet mononuclear cell infiltration without evidence of rejection. Discussion: The perihepatic surface serves as a viable site for islet cell transplantation demonstrating sustained islet function through 6 months. The targeted mapping approach allows for the testing of multiple conditions simultaneously to evaluate immune response to biomaterials at this site. Compared to traditional intraportal injection, the perihepatic site is a minimally invasive approach that allows the possibility for graft recovery and avoids IBMIR.

A Hospice Transitions Program for Patients in the Emergency Department.

Importance: Patients often visit the emergency department (ED) near the end of life. Their common disposition is inpatient hospital admission, which can result in a delayed transition to hospice care and, ultimately, an inpatient hospital death that may be misaligned with their goals of care. Objective: To assess the association of hospice use with a novel multidisciplinary hospice program to rapidly identify and enroll eligible patients presenting to the ED near end of life. Design, Setting, and Participants: This pre-post quality improvement study of a novel, multifaceted care transitions program involving a formalized pathway with email alerts, clinician training, hospice vendor expansion, metric creation, and data tracking was conducted at a large, urban tertiary care academic medical center affiliated with a comprehensive cancer center among adult patients presenting to the ED near the end of life. The control period before program launch was from September 1, 2018, to January 31, 2020, and the intervention period after program launch was from August 1, 2021, to December 31, 2022. Main Outcome and Measures: The primary outcome was a transition to hospice without hospital admission and/or hospice admission within 96 hours of the ED visit. Secondary outcomes included length of stay and in-hospital mortality. Results: This study included 270 patients (median age, 74.0 years [IQR, 62.0-85.0 years]; 133 of 270 women [49.3%]) in the control period, and 388 patients (median age, 73.0 years [IQR, 60.0-84.0 years]; 208 of 388 women [53.6%]) in the intervention period, identified as eligible for hospice transition within 96 hours of ED arrival. In the control period, 61 patients (22.6%) achieved the primary outcome compared with 210 patients (54.1%) in the intervention period (P < .001). The intervention was associated with the primary outcome after adjustment for age, race and ethnicity, primary payer, Charlson Comorbidity Index, and presence of a Medical Order for Life-Sustaining Treatment (MOLST) (adjusted odds ratio, 5.02; 95% CI, 3.17-7.94). In addition, the presence of a MOLST was independently associated with hospice transition across all groups (adjusted odds ratio, 1.88; 95% CI, 1.18-2.99). There was no significant difference between the control and intervention periods in inpatient length of stay (median, 2.0 days [IQR, 1.1-3.0 days] vs 1.9 days [IQR, 1.1-3.0 days]; P = .84), but in-hospital mortality was lower in the intervention period (48.5% [188 of 388] vs 64.4% [174 of 270]; P < .001). Conclusions and Relevance: In this quality improvement study, a multidisciplinary program to facilitate ED patient transitions was associated with hospice use. Further investigation is needed to examine the generalizability and sustainability of the program.

A Plain Language Summary of "Dostarlimab for primary advanced or recurrent endometrial cancer".

What is this summary about? Dostarlimab, also known by the brand name JEMPERLI, is a medicine that uses a patient's own immune system to treat endometrial cancer. Dostarlimab is a type of medicine called an immunotherapy. Immunotherapies help the immune system find and attack cancer cells. Dostarlimab stops cancer cells from being able to hide from the immune system, which allows the patient to have a boosted immune response against their cancer.The RUBY study is a phase 3 clinical study of primary advanced (cancer that has spread outside the uterus) or recurrent (cancer that has come back) endometrial cancer. A phase 3 clinical study looks at how well a new treatment works compared to the standard, or usual, treatment in a large patient population. The RUBY study is testing how well dostarlimab given with chemotherapy, followed by dostarlimab alone, works at delaying primary advanced or recurrent endometrial cancer from getting worse and preventing patients from dying, compared to chemotherapy given alone (the current standard treatment for primary advanced or recurrent endometrial cancer).What were the results? When dostarlimab was given with chemotherapy, this combination was found to delay primary advanced or recurrent endometrial cancer from getting worse and to prevent patients from dying, compared with chemotherapy given alone (without dostarlimab). Patients in the study who received dostarlimab with chemotherapy had a 36% lower risk of dying or having their cancer get worse.What do the results mean? The results from this study contributed to the approval of dostarlimab with chemotherapy as a new treatment option for patients with mismatch repair deficient/microsatellite instability-high primary advanced or recurrent endometrial cancer. As of the publication of this plain language summary of publication (PLSP), this combination of dostarlimab with chemotherapy has been approved in the United States of America, the United Kingdom, the European Union and Hong Kong.Clinical Trial Registration: NCT03981796 (RUBY).

Tolerability of the niraparib individualized starting dose in the PRIMA/ENGOT-OV26/GOG-3012 trial of niraparib first-line maintenance therapy.

PURPOSE: To explore safety and tolerability parameters for the niraparib individualized starting dose (ISD) in patients with newly diagnosed advanced ovarian cancer that responded to platinum-based chemotherapy who participated in the phase 3 PRIMA/ENGOT-OV26/GOG-3012 trial (NCT02655016). METHODS: The PRIMA protocol was amended so newly enrolled patients received an ISD based on baseline body weight/platelet count. In this ad hoc analysis, the timing, duration, and resolution of the first occurrence of common any-grade hematologic (thrombocytopenia, anemia, neutropenia) and nonhematologic (nausea, asthenia/fatigue, constipation, insomnia, hypertension) treatment-emergent adverse events (TEAEs) were evaluated by treatment arm in the ISD safety population (data cutoff, November 17, 2021; median follow-up, 3.5 years). RESULTS: Of 733 randomized patients, 255 were enrolled after the ISD protocol amendment and received ≥ 1 dose of study treatment (niraparib, 169; placebo, 86). In the niraparib arm, median times to first events were 22.0-35.0 days for hematologic TEAEs and 7.0-56.0 days for nonhematologic TEAEs. First events resolved in ≥ 89.8% of patients for hematologic TEAEs; for nonhematologic TEAEs, resolution rates ranged from 55.3% (insomnia) to 86.0% (nausea). Median durations of first hematologic TEAEs were ≤ 16.0 days, but for first nonhematologic TEAEs ranged from 18.0 days (nausea) to 134.0 days (insomnia). CONCLUSION: The niraparib ISD was generally well tolerated and TEAEs were manageable. Common hematologic and nonhematologic TEAEs occurred early and first events of hematologic TEAEs had a short duration (≈ 2 weeks) and a high resolution rate. These findings support close monitoring immediately following niraparib initiation and may help inform patient expectations for niraparib safety.

Preinjection With Ligation-Assisted Endoscopic Mucosal Resection for Barrett's Dysplasia and Early Esophageal Adenocarcinoma: Characteristic Histological Features of the Depth of Resection.

BACKGROUND AND AIM: Endoscopic mucosal resection (EMR) is an established technique for the diagnosis and treatment of high-grade dysplasia (HGD) and early esophageal adenocarcinoma (EAC) in Barrett's esophagus. Submucosal preinjection is not universally used or generally recommended when performing routine ligation-assisted EMR. Prior studies, however, have demonstrated evidence of at least superficial muscle injury on ligation-assisted EMR without submucosal injection. There are limited published data supporting any potential benefit of submucosal preinjection. Our aim was to review this technique and determine the rate of any degree of muscle injury in patients with Barrett's HGD and EAC treated with submucosal preinjection before ligation-assisted EMR. METHODS: Patients undergoing submucosal preinjection before ligation-assisted EMR for Barrett's esophagus at a single institution between 2012 and 2016 were identified. Data were collected regarding patient demographics and medical history, endoscopy and histopathology findings, adverse events, and subsequent outcomes. All EMR specimens were reviewed by an expert gastrointestinal pathologist. RESULTS: One hundred fifty consecutive EMR procedures were performed on 70 patients. Of 70 patients, 85.7% of patients were men, with a median age of 68 years. EAC was identified in 75 specimens (50%) and HGD in 44 specimens (29.3%). Deep resection margins were clear of adenocarcinoma in all specimens. Muscularis propria was not identified in any of the 150 specimens. There were no cases of post-EMR perforation. CONCLUSIONS: Preinjection before ligation-assisted EMR achieved complete excision with histologically clear margins, without histological evidence of any inadvertent muscularis propria.

A non-comparative, randomized, phase II trial of atezolizumab or atezolizumab plus tiragolumab for programmed death-ligand 1-positive recurrent cervical cancer (SKYSCRAPER-04).

OBJECTIVE: To evaluate tiragolumab (anti-TIGIT) and atezolizumab (anti-PD-L1) as second- or third-line therapy for PD-L1-positive persistent/recurrent cervical cancer. METHODS: In the open-label, non-comparative, randomized phase II SKYSCRAPER-04 trial (NCT04300647), patients with PD-L1-positive (SP263 tumor area positivity ≥5%) recurrent/persistent cervical cancer after 1-2 chemotherapy lines (≥1 platinum-based) were randomized 3:1 to atezolizumab 1200 mg with/without tiragolumab 600 mg every 3 weeks until disease progression or unacceptable toxicity. Stratification factors were performance status, prior (chemo)radiotherapy, and disease status. The primary endpoint was independent review committee-assessed confirmed objective response rate per RECIST v1.1 in patients receiving tiragolumab plus atezolizumab. An objective response rate ≥21% (one-sample z-test p≤0.0245) was required for statistical significance versus a historical reference. RESULTS: Protocol-defined independent review committee-assessed objective response rates were 19.0% (95% CI 12.6 to 27.0) in 126 patients receiving tiragolumab plus atezolizumab (p=0.0787 vs historical reference) and 15.6% (95% CI 6.5 to 29.5) in 45 atezolizumab-treated patients. Response rates were higher in PD-L1high (tumor area positivity ≥10%) than PD-L1low (tumor area positivity 5%-9%) subgroups with both regimens. At 8.5 months' median follow-up, independent review committee-assessed progression-free survival was 2.8 months (95% CI 1.7 to 4.1) with tiragolumab plus atezolizumab and 1.9 months (95% CI 1.5 to 3.0) with atezolizumab. In post hoc analyses (10.4 months' median follow-up), median overall survival was 11.1 months (95% CI 9.6 to 14.5) with the combination and 10.6 months (95% CI 6.9 to 13.8) with atezolizumab (crossover permitted). In the combination group, 3% of patients had adverse events requiring treatment discontinuation and 8% had grade ≥3 adverse events of special interest; corresponding values in the single-agent arm were 4% and 11%. There were no treatment-related deaths or new safety findings. CONCLUSION: The objective response rate with the tiragolumab-plus-atezolizumab combination was numerically higher than the historical reference but did not reach statistical significance.

Correlative multimodal optical and X-ray fluorescence imaging of brominated fluorophores.

Imaging with multiple modalities can maximise the information gained from the analysis of a single sample. probes for optical fluorescence and X-ray fluorescence microscopy based on brominated 4-amino-1,8-naphthalimide and BODIPY scaffolds have been successfully designed and synthesised. Herein we show that these prototype probes, based on each of these scaffolds, can be imaged in two different cancer cell lines, and that the respective optical fluorescence and X-ray fluorescence signals are well correlated in these images.

Exploring the effect of domain-specific transfer learning for thyroid nodule classification.

Thyroid nodule evaluation using ultrasound is dependent on radiologist experience, but deep learning (DL) models can improve intra-reader agreements. DL model development for medical imaging with small datasets can be challenging. Transfer learning is a technique used in the development of DL models to improve model performance in data-limited scenarios. Here, we investigate the impact of transfer learning with domain-specific RadImageNet dataset and non-medical ImageNet on the robustness of classifying thyroid nodules into benign and malignant. We retrospectively collected 822 ultrasound images of thyroid nodules of patients who underwent fine needle aspiration in our institute. We split our data and used 101 cases in a test set and 721 cases for cross-validation. A Resnet-18 model was trained to classify thyroid nodules into benign and malignant. Then, we trained the same model architecture with transferred weights from ImageNet and RadImageNet. The model without transfer learning for thyroid nodule classification achieved an AUROC of 0.69. The AUROC of our model after transfer learning with ImageNet pre-trained weights was 0.79. Our model achieved an AUROC of 0.83 from transfer learning of the RadImageNet pre-trained weights. The AUROC from the classification model without transfer learning significantly improved after transfer learning with ImageNet (p-value = 0.03) and RadImageNet transfer learning (p-value <0.01). There was a statistically significant distinction in performance between the model utilizing RadImageNet transfer learning and that employing ImageNet transfer learning (p-value <0.01). We demonstrate the potential of RadImageNet as a domain-specific source for transfer learning in thyroid nodule classification.

Whole-body low-dose computed tomography in patients with newly diagnosed multiple myeloma predicts cytogenetic risk: a deep learning radiogenomics study.

OBJECTIVE: To develop a whole-body low-dose CT (WBLDCT) deep learning model and determine its accuracy in predicting the presence of cytogenetic abnormalities in multiple myeloma (MM). MATERIALS AND METHODS: WBLDCTs of MM patients performed within a year of diagnosis were included. Cytogenetic assessments of clonal plasma cells via fluorescent in situ hybridization (FISH) were used to risk-stratify patients as high-risk (HR) or standard-risk (SR). Presence of any of del(17p), t(14;16), t(4;14), and t(14;20) on FISH was defined as HR. The dataset was evenly divided into five groups (folds) at the individual patient level for model training. Mean and standard deviation (SD) of the area under the receiver operating curve (AUROC) across the folds were recorded. RESULTS: One hundred fifty-one patients with MM were included in the study. The model performed best for t(4;14), mean (SD) AUROC of 0.874 (0.073). The lowest AUROC was observed for trisomies: AUROC of 0.717 (0.058). Two- and 5-year survival rates for HR cytogenetics were 87% and 71%, respectively, compared to 91% and 79% for SR cytogenetics. Survival predictions by the WBLDCT deep learning model revealed 2- and 5-year survival rates for patients with HR cytogenetics as 87% and 71%, respectively, compared to 92% and 81% for SR cytogenetics. CONCLUSION: A deep learning model trained on WBLDCT scans predicted the presence of cytogenetic abnormalities used for risk stratification in MM. Assessment of the model's performance revealed good to excellent classification of the various cytogenetic abnormalities.

Prostatic Utricle Cysts as a Potential Pitfall in PSMA PET/CT Interpretation.

ABSTRACT: A 60-year-old man with T2aN0M0 prostate cancer underwent intensity-modulated radiotherapy targeting the prostate and seminal vesicles. Experiencing biochemical recurrence after 6 years, 68Ga-PSMA-11 PET/CT revealed focal radioactivity in the posterior midline of the prostate, identified as a prostatic utricle cyst on subsequent MRI. Similar findings appeared in a previous 18F-piflufolastat PET/CT, with negative biopsy results. The patient then received intensity-modulated radiotherapy directed to 2 PSMA-avid pelvic nodes and leuprolide acetate, achieving an undetectable PSA in 4 months. This case highlights a potential pitfall in PSMA PET interpretation associated with prostatic utricle cysts.

Adjunctive Dorsal Spanning Plate Fixation in the Stabilization of Perilunate Dislocations.

PURPOSE: To compare the biomechanical properties of adjunctive dorsal spanning plate (DSP) fixation with traditional K-wire fixation of perilunate dislocations in a cadaveric model. METHODS: Fourteen fresh-frozen cadaveric wrists underwent simulated perilunate injury. The specimens were randomly allocated to either K-wire fixation versus K-wire and DSP fixation. Scapholunate (SL) ligament repair was performed in all specimens. The constructs were tested using a robot cyclically and to failure. Fluoroscopic images were obtained of the specimens prior to simulated injury, after fixation, after 10 and 100 loading cycles, and at construct failure. Differences in carpal alignment parameters (SL interval, SL angle, lunotriquetral interval, and capitolunate angle) and load to failure were recorded. RESULTS: There were no statistically significant differences between the two group's carpal alignment parameters after fixation. Specimens fixated with K-wires and DSP required significantly higher loads to achieve construct failure. The only significant difference between the two groups' carpal alignment parameters was SL interval change at failure. CONCLUSIONS: Compared with K-wire fixation alone, adjunctive DSP fixation resulted in significantly increased loads to failure and decreased change in SL interval at the time of failure. CLINICAL RELEVANCE: Adjunctive DSP may be a useful technique in the polytraumatized patient in whom providing back a weight-bearing extremity may be advantageous in the rehabilitation process.

Prostate Cancer Lung Metastasis: Clinical Insights and Therapeutic Strategies.

Prostate cancer lung metastasis represents a clinical conundrum due to its implications for advanced disease progression and the complexities it introduces in treatment planning. As the disease progresses to distant sites such as the lung, the clinical management becomes increasingly intricate, requiring tailored therapeutic strategies to address the unique characteristics of metastatic lesions. This review seeks to synthesize the current state of knowledge surrounding prostate cancer metastasis to the lung, shedding light on the diverse array of clinical presentations encountered, ranging from subtle radiological findings to overt symptomatic manifestations. By examining the diagnostic modalities utilized in identifying this metastasis, including advanced imaging techniques and histopathological analyses, this review aims to provide insights into the diagnostic landscape and the challenges associated with accurately characterizing lung metastatic lesions in prostate cancer patients. Moreover, this review delves into the nuances of therapeutic interventions employed in managing prostate cancer lung metastasis, encompassing systemic treatments such as hormonal therapies and chemotherapy, as well as metastasis-directed therapies including surgery and radiotherapy.

Joint association of drinking alcohol and obesity in relation to cancer risk: A systematic review and data synthesis.

BACKGROUND: Rates of alcohol consumption and obesity are increasing in many Western populations. For some cancer types, both heavy alcohol consumption and obesity are independently associated with increased risk. Whether combined exposure to both synergistically increases an individual's risk of cancer is unclear. We performed a systematic review to assess whether alcohol and obesity interact to confer higher risk for cancer than the additive sum of their effects. METHODS: A systematic literature search was conducted from the inception date to 13 February 2024 of PubMed, Embase, Cochrane Library and Web of Science to identify studies of alcohol, obesity, and cancer risk. We aimed to undertake a meta-analysis if there were sufficient data. RESULTS: The literature search identified 17,740 potentially eligible studies. After review, 24 studies were included. Eleven reported on the association between alcohol consumption and cancer risk in individuals according to their body mass index (BMI), nine reported on the association between BMI and cancer risk in individuals according to their alcohol consumption, and six studies examined potential synergistic interactions between alcohol consumption and obesity on cancer risk. However, there were insufficient data and significant heterogeneity in the cancers studied to undertake meta-analysis, therefore a systemic review and narrative synthesis was conducted. Overall, there was no consistent pattern of interaction between alcohol use and overweight/obesity on cancer risk across cancer types. CONCLUSIONS: While alcohol and obesity are prevalent and important risk factors for a range of cancers, data are lacking on whether their combined exposure may synergistically increase an individual's risk for cancer. Further study across more cancer types is required to better understand the nature of interactions between alcohol use and obesity on cancer risk.

Standardized evaluation of the extent of resection in glioblastoma with automated early post-operative segmentation.

Standard treatment of patients with glioblastoma includes surgical resection of the tumor. The extent of resection (EOR) achieved during surgery significantly impacts prognosis and is used to stratify patients in clinical trials. In this study, we developed a U-Net-based deep-learning model to segment contrast-enhancing tumor on post-operative MRI exams taken within 72 h of resection surgery and used these segmentations to classify the EOR as either maximal or submaximal. The model was trained on 122 multiparametric MRI scans from our institution and achieved a mean Dice score of 0.52 ± 0.03 on an external dataset (n = 248), a performance -on par with the interrater agreement between expert annotators as reported in literature. We obtained an EOR classification precision/recall of 0.72/0.78 on the internal test dataset (n = 462) and 0.90/0.87 on the external dataset. Furthermore, Kaplan-Meier curves were used to compare the overall survival between patients with maximal and submaximal resection in the internal test dataset, as determined by either clinicians or the model. There was no significant difference between the survival predictions using the model's and clinical EOR classification. We find that the proposed segmentation model is capable of reliably classifying the EOR of glioblastoma tumors on early post-operative MRI scans. Moreover, we show that stratification of patients based on the model's predictions offers at least the same prognostic value as when done by clinicians.

Dosimetric Features of Ultra-Hypofractionated Intensity Modulated Proton Therapy for Prostate Cancer.

Purpose: To report clinical and dosimetric characteristics of 5-fraction stereotactic ablative radiotherapy (SABR) using intensity modulated proton therapy (IMPT) for localized prostate cancer. Materials and Methods: All patients receiving IMPT SABR from 2017 to 2021 for localized prostate cancer at our institution were included. Five fractions were delivered every other day to the prostate +/- seminal vesicles [clinical target volume (CTV)] with 3 mm/3% robustness. A 4-field arrangement with 2 anterior oblique and 2 opposed lateral beams was used in most patients (97%), and most (99%) had a retroprostatic hydrogel spacer. Results: A total of 534 patients with low (14%), favorable intermediate (45%), unfavorable intermediate (36%), high (4.0%), or very high-risk (0.6%) disease are evaluated. Prescription dose was 36.25 Gy (31%), 38 Gy (38%), or 40 Gy (31%) was prescribed. Median volume percentage of CTV receiving at least 100% of prescription dose [V100% (%)] was 100% [interquartile range: 99.99-100]. Rectum V50% (%), V80% (%), and V90% (%) were significantly lower in patients who had spacer, with a mean difference of -9.70%, -6.59%, and -4.42%, respectively, compared to those who did not have spacer. Femoral head dose was lower with a 4-field arrangement. Mean differences in left and right femoral head V40% (%) were -6.99% and -10.74%, respectively. Conclusion: We provide a large, novel report of patients treated with IMPT SABR for localized prostate cancer. Four-field IMPT with hydrogel spacer provides significant sparing of rectum and femoral heads without compromising target coverage.