Guide Treatment Selection Research Articles

Diverse RNA methylation patterns in neutrophils: key drivers in hepatocellular carcinoma.

Neutrophils, crucial in the immune system, have recently been implicated in promoting malignancy. RNA methylation, an essential epigenetic feature, plays a key role in tumor microenvironment (TME) reprogramming. However, the relationship between neutrophils and RNA methylation in hepatocellular carcinoma (HCC) remains unclear. We analyzed single-cell sequencing data from HCC, focusing on cell subtype and TME construction. RNA methylation "writers" were selected, and their expression in neutrophils was evaluated. Two neutrophil subtypes (high/low RNA methylation) were identified. Differentially expressed genes (DEGs) between these subtypes were confirmed, leading to the identification of 6 molecular subtypes via consensus clustering. A prognostic scoring system was developed using LASSO Cox regression, resulting in a novel neutrophil RNA methylation (NRM) scoring system to assess TME heterogeneity and clinical features. TRPM3, specifically expressed in HCC-infiltrating neutrophils, may regulate RNA modification in tumor pathogenesis. HCC patients were stratified into low/high-NRM score groups, further refined into an advanced NRM (a-NRM) score by incorporating lncRNA data. High a-NRM scores correlated with advanced TNM stage, higher pathological grade, and increased suppressive immune cells. A nomogram incorporating the a-NRM score demonstrated a concordance index indicative of good predictive performance. The a-NRM score is a reliable predictor of prognosis and could guide treatment selection in HCC patients, enhancing clinical response to immunotherapy. TRPM3 also presents as a potential therapeutic target in HCC.

Prostatectomy and other local treatments for oligometastatic prostate cancer: recent and ongoing trials.

Oligometastatic prostate cancer (OMPCa) is an intermediary state between localized and disseminated metastatic disease that has historically been treated with androgen deprivation therapy (ADT) and more recently with additional systemic therapies in combinations. However, cytoreductive control of the primary tumor may offer an opportunity to control the disease and enhance the response from systemic treatment. In this review, the use of local therapy to the prostate including cytoreductive prostatectomy (CRP), whole pelvis radiotherapy (RT), and focal therapies will be evaluated in the treatment of patients with newly diagnosed OMPCa. Retrospective studies have demonstrated that some patients with OMPCa may indeed benefit from CRP. With preliminary trials demonstrating that CRP is safe and feasible, there are several phase II and III trials that are currently underway to investigate the role of CRP among patients with OMPCa. Results from several clinical trials have demonstrated that RT and ADT may benefit patients with OMPCa. Lastly, the evidence for focal and cryotherapy remains limited and further clinical trials are required. OMPCa is a unique disease state that may benefit from local therapy to the primary tumor. Further study is required to guide treatment selection and patient candidacy. Several trials specifically are awaited to better define the treatment options for patients.

The Added Value of Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography to Magnetic Resonance Imaging for Local Staging of Prostate Cancer in Patients Undergoing Radical Prostatectomy

Background and objectiveThe role of prostate-specific membrane antigen (PSMA)-based positron emission tomography (PET)/computed tomography (CT) in addition to magnetic resonance imaging (MRI) for local staging of prostate cancer (PC) has been poorly addressed so far. Our aim was to assess the diagnostic accuracy of PSMA PET/CT and MRI, alone and combined, for detection of extraprostatic extension (EPE) and seminal vesicle invasion (SVI) in PC. MethodsWe conducted a multicenter retrospective study evaluating patients undergoing PSMA PET/CT and MRI before radical prostatectomy. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC) for detection of EPE and SVI were calculated for MRI and PSMA PET/CT alone and combined. Key findings and limitationsWe included 550 patients, of whom 2%, had low-risk, 43% had intermediate-risk, and 55% had high-risk PC. Overall, 52% of patients had EPE and 21% had SVI at histopathology. Patient-based comparison of MRI versus PSMA PET/CT for detection of EPE revealed sensitivity of 60% versus 41% (p < 0.001), specificity of 77% versus 83% (p = 0.075), PPV of 75% versus 73% (p = 0.6), NPV of 64% versus 56% (p < 0.001), and AUC of 69% versus 62% (p = 0.01). Combining the modalities increased the sensitivity (73%; p < 0.001) and NPV (69%; p < 0.001) and decreased the specificity (67%; p < 0.001) and PPV (71%; p = 0.01) over MRI alone. Patient-based comparison of MRI versus PSMA PET/CT for detection of SVI revealed sensitivity of 36% versus 44% (p = 0.2), specificity of 96% versus 96% (p > 0.99), PPV of 71% versus 75% (p = 0.6), NPV of 85% versus 87% (p = 0.2), and AUC of 66% versus 70% (p = 0.2). Combining the modalities increased the sensitivity (60%; p < 0.001), NPV (90%; p < 0.001), and AUC (76%; p < 0.001) and decreased the specificity (92%; p < 0.001) over MRI alone. Limitations include the retrospective nature of the study, selection of higher-risk cases for PSMA PET/CT, and lack of central review. Conclusions and clinical implicationsPSMA PET/CT has lower sensitivity for EPE detection in comparison to MRI. However, addition of PSMA PET information to MRI improved the sensitivity for EPE and SVI detection. Thus, the two modalities should be combined to guide treatment selection. Patient summaryCombining MRI (magnetic resonance imaging) scans with another type of imaging called PSMA PET/CT (prostate-specific membrane antigen positron emission tomography/computed tomography) for patients with prostate cancer leads to better identification of cancer growth outside the prostate in comparison to MRI alone. This could potentially improve the choice of prostate cancer treatment.

Identification and Characterization of a Novel CCDC6::CASP7 Gene Rearrangement in an Advanced Colorectal Cancer Patient: A Case Report

Despite the existence of effective therapy options for patients with localized colorectal cancer, advanced-stage patients have limited therapies. Genomic profiling is a promising tool for guiding treatment selection as well as patient monitoring. Here, we describe a novel gene rearrangement (CCDC6::CASP7) detected in a patient with advanced colorectal cancer that could be a therapeutic target. The patient underwent surgical resection but died after the operation from fecal peritonitis. To our knowledge, this is the first report in which the CCDC6::CASP7 gene rearrangement has been described in an advanced colorectal adenocarcinoma patient.

Identifying immunohistochemical biomarkers panel for non-small cell lung cancer in optimizing treatment and forecasting efficacy

BackgroundChemotherapy and immunotherapy for non-small-cell lung cancer (NSCLC) are gaining momentum. However, its long-term efficacy remains limited to only a small fraction of patients. Hence, it is crucial to identify reliable immunohistochemical biomarkers to facilitate the formulation of optimal treatment strategies and to predict therapeutic outcomes.MethodsWe retrospectively analyzed a cohort of 140 patients diagnosed with NSCLC who received chemotherapy or immunotherapy. Using bioinformatics analysis and machine learning techniques, we assessed the role of immunohistochemical biomarkers and clinical characteristics in developing a predictive model for treatment options and outcomes in this population.ResultsOur research has found that immunohistochemical biomarkers can accurately predict treatment regimens and progression-free survival in NSCLC patients with an accuracy rate of 82.1%. We identified an exclusive detection panel for the six vital biomarkers. Of particular note is the role of programmed cell death protein 1 ligand 1 (PD-L1) expression in guiding treatment selection, with high expression predicting better outcomes in the immunotherapy group at a cut-off value of 50%. Non-squamous patients who tested positive for thyroid transcription factor 1 had a longer median progression-free survival, while squamous patients who tested positive for p63 protein or cytokeratin 5/6 expression had a longer median progression-free survival.ConclusionsThe results of our study are highly encouraging, as they revealed a significant correlation between immunohistochemical biomarkers, therapeutic regimens, and prognosis. These findings indicate that our immunohistochemical detection panel has great potential for facilitating customization of therapeutic regimens to improve patient care. The insights gained from this study could help clinicians optimize treatment protocols and ultimately enhance clinical outcomes.

FRENULECTOMY OF SHORT FRENULUMS OF THE UPPER LIP IN THE TREATMENT OF DIASTEMAS IN CHILDREN

Objective: This study examines the relevance and necessity of addressing upper lip frenulum abnormalities in pediatric patients, given the increasing incidence due to environmental factors, dietary additives, and structural predispositions affecting periodontal health. Methods: Clinical studies and literature systematizations were reviewed to classify frenulum abnormalities and evaluate frenuloplasty techniques. Notable classifications include the morphological and attachment-based categorization by Nenashev and Kulikov and the density differentiation by Obraztsov and Larionov. Methods from Khoroshilkina, particularly the Limberg and Popovich techniques, are discussed for their effectiveness in managing frenulum-related diastemas. Results: The study highlights the efficacy of these frenuloplasty techniques, which involve either triangular flap repositioning (Limberg) or frenulum edge relocation to the transitional fold (Popovich). These methods have been demonstrated to effectively prevent and manage dentoalveolar deformities in outpatient settings. Novelty: This research underscores the need for an algorithm to guide treatment selection and optimize surgical outcomes based on individual frenulum morphology and attachment. Implications: The findings inform pediatric surgical dentistry, suggesting a structured approach to frenulum treatment to prevent progressive periodontal issues, speech impediments, and developmental irregularities in the dentofacial system. Further research should explore standardized protocols for surgical intervention selection in pediatric patients.

Navigating therapeutic sequencing in the metastatic castration-resistant prostate cancer patient journey.

Novel therapies for metastatic castration-resistant prostate cancer (mCRPC) have improved patient outcomes. However, there is uncertainty on the optimal selection of therapeutic agents for subsequent lines of therapy. We conducted a comprehensive review of published evidence from pivotal clinical trials and recent guidelines for the treatment of mCRPC. We further identify gaps in knowledge and areas for future research. Key considerations to help guide treatment selection for patients with mCRPC include personal treatment history, individual clinical characteristics, symptoms, prognosis, availability of clinical trials, and other patient-specific factors. Genetic testing and prostate-specific membrane antigen-targeted imaging are important tools to evaluate candidacy for newer therapeutic options such as poly (ADP-ribose) polymerase inhibitors, alone or in combination with androgen receptor pathway inhibitors, and [177Lu]Lu-PSMA-617. This article provides an overview of the evolving treatment landscape of mCRPC, discussing guideline-recommended treatment options and data from key clinical trials, while highlighting ongoing trials that may impact the future treatment landscape. Recommendations for optimal treatment sequencing based on individual patient factors are provided.

Challenges in implementation of molecular classification in early stage endometrial cancer-An NRG Oncology cooperative group mixed-methods study.

Professional guidelines recommend molecular profiling for mismatch repair (MMR), p53, and polymerase epsilon (POLE) status in endometrial cancer (EC). However, adoption in the United States has not been documented, and barriers to the implementation of testing have not been described. In this mixed-methods study, implementation science frameworks were used to develop a quantitative survey. Gynecologic oncologists, medical oncologists, radiation oncologists, and pathologists affiliated with NRG Oncology programs were contacted through snowball sampling and were surveyed during 2022-2023. A subset of respondents was interviewed. Statistical and thematic analyses were performed. At least 403 NRG Oncology-affiliated providers were contacted for the survey, and 107 (26.6%) responded. Greater than 90% of respondents perceived POLE, MMR, and p53 status as important for clinical care. MMR and p53 tests were perceived as easy to obtain, but only 24.2% of respondents reported that POLE testing was moderately or very easy to obtain. Respondents from academic sites reported better access to molecular classification and perceived greater importance of molecular classification compared with respondents from community sites. In thematic analysis of 13 qualitative interviews, cost concerns were reported as large barriers to testing. Interviewees reported a desire for prospective data to guide treatment selection based on classification results. Although integrating molecular classification into standard pathologic reporting is recommended, and clinicians perceive molecular profiling in early stage EC as important, survey respondents noted significant implementation barriers. Implementation challenges that differ between community oncology and academic practice settings were identified. Strategies to improve equitable access to molecular classification of early stage EC are needed.

Construction and validation of a pancreatic cancer prognostic model based on genes related to the hypoxic tumor microenvironment.

Pancreatic cancer is one of the most lethal malignancies, characterized by poor prognosis and low survival rates. Traditional prognostic factors for pancreatic cancer offer inadequate predictive accuracy, often failing to capture the complexity of the disease. The hypoxic tumor microenvironment has been recognized as a significant factor influencing cancer progression and resistance to treatment. This study aims to develop a prognostic model based on key hypoxia-related molecules to enhance prediction accuracy for patient outcomes and to guide more effective treatment strategies in pancreatic cancer. To develop and validate a prognostic model for predicting outcomes in patients with pancreatic cancer using key hypoxia-related molecules. This pancreatic cancer prognostic model was developed based on the expression levels of the hypoxia-associated genes CAPN2, PLAU, and CCNA2. The results were validated in an independent dataset. This study also examined the correlations between the model risk score and various clinical features, components of the immune microenvironment, chemotherapeutic drug sensitivity, and metabolism-related pathways. Real-time quantitative PCR verification was conducted to confirm the differential expression of the target genes in hypoxic and normal pancreatic cancer cell lines. The prognostic model demonstrated significant predictive value, with the risk score showing a strong correlation with clinical features: It was significantly associated with tumor grade (G) (b P < 0.01), moderately associated with tumor stage (T) (a P < 0.05), and significantly correlated with residual tumor (R) status (b P < 0.01). There was also a significant negative correlation between the risk score and the half-maximal inhibitory concentration of some chemotherapeutic drugs. Furthermore, the risk score was linked to the enrichment of metabolism-related pathways in pancreatic cancer. The prognostic model based on hypoxia-related genes effectively predicts pancreatic cancer outcomes with improved accuracy over traditional factors and can guide treatment selection based on risk assessment.

Harnessing nucleotide metabolism and immunity in cancer: a tumour microenvironment perspective

The tumour microenvironment (TME) is a dynamic nexus where cancer cell metabolism and the immune system intricately converge, with nucleotide metabolism (NM) playing a pivotal role. This review explores the critical function of NM in cancer cell proliferation and its profound influence on the TME and immune landscape. NM is essential for DNA and RNA synthesis and is markedly upregulated in cancer cells to meet the demands of rapid growth. This metabolic rewiring fuels cancer progression, but also shapes the TME, impacting the function and viability of immune cells. The altered nucleotide milieu in the TME can suppress immune response, aiding cancer cell evasion from immune surveillance. Drug discoveries in the field of NM have revealed different therapeutic strategies, including inhibitors of nucleotide synthesis and drugs targeting salvage pathways, which are discussed thoroughly in this review. Furthermore, the emerging strategy of combining NM‐targeted therapies with immunotherapies is emphasised, particularly their effect on sensitising tumours to immune checkpoint inhibitors and enhancing overall treatment efficacy. The Human Genome Project paved the way for personalised medicine, countering the established ‘one size fits all’ approach to cancer treatment. Advances in understanding the TME and NM have spurred interest in personalised therapeutic strategies. This review highlights the potential of leveraging individual tumour metabolic profiles to guide treatment selection, aiming to optimise efficacy and minimise adverse effects. The strategic importance of targeting NM in cancer therapy and its synergistic potential with immunotherapies offers a path towards more effective and personalised cancer treatments.

Abstract A013: Advanced Gene Signatures for the Diagnosis and Personalized Treatment of Pancreatic Ductal Adenocarcinoma

Abstract Pancreatic ductal adenocarcinoma (PDA) is among the most lethal tumors, with limited treatment options. The absence of reliable screening and diagnostic tools (biomarkers or procedures) significantly contributes to its poor prognosis. Biomarkers that can diagnose PDA, select optimal therapy combinations, and predict the risk of occult metastases are crucial for enhancing treatment outcomes. Previously, we identified methylation signatures capable of predicting outcomes and diagnosing PDA, focusing on genes/proteins with preclinical evidence of influencing key drugs (gemcitabine [Gem], 5-fluorouracil [5FU], oxaliplatin, cisplatin, paclitaxel, and irinotecan) used in treatment. To make these findings more clinically applicable and propose a novel approach for personalized treatment selection between Gem-based (Gem/nab-paclitaxel) and 5FU-based (FOLFIRINOX) combinations, we explored the diagnostic value of genes associated specifically with Gem and 5FU. The objective was to develop a gene signature for diagnosing PDA and aiding in treatment selection. Based on recent literature, we updated our previous gene panels (from 55 to 93 for Gem, and from 20 to 28 for 5FU). We analyzed RNA and gene expression differences between normal (NT) and PDA tissues using TNMplot.com, a web tool that leverages data from the Gene Expression Omnibus (NCBI-GEO), Cancer Genome Atlas (TCGA), Therapeutically Applicable Research to Generate Effective Treatments (TARGET), and The Genotype-Tissue Expression (GTEx) repositories, employing Mann-Whitney or Kruskal-Wallis tests for statistical significance. For the Gem-specific gene panel, the combined RNA expression of 90 out of 93 genes was significantly higher in PDA compared to NT (2.59, p=6.48e-61), while the combined gene expression of 80 out of 93 genes was also significantly higher in PDA tissues (1.62, p=3.48e-29). For the 5FU-specific gene panel, the combined RNA expression of 27 out of 28 genes was significantly elevated in PDA (2.00, p=5.44e-57), and the combined gene expression of 23 out of 28 genes was significantly higher in PDA tissues (1.21, p=1.44e-7). Our preliminary findings suggest that this approach has the potential to serve as an effective tool for diagnosing PDA and guiding treatment selection. However, these results must be validated through larger prospective studies. Additionally, this application could serve as a screening tool for high-risk populations, such as individuals with potentially malignant lesions like intraductal papillary mucinous neoplasms, first-degree relatives of PDA patients, or those with concerning genetic risks (e.g., BRCA1 or BRCA2 mutations). Citation Format: Harshitha Puram, Deepak Sherpally, Sravan Jeepalyam, Ashish Manne. Advanced Gene Signatures for the Diagnosis and Personalized Treatment of Pancreatic Ductal Adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr A013.

Choosing Wisely Between Radiotherapy Dose-Fractionation Schedules: The Molecular Graded Prognostic Assessment for Elderly Glioblastoma Patients.

This study aimed to develop a graded prognostic assessment (GPA) model integrating genomic characteristics for elderly patients with glioblastoma (eGBM), and to compare the efficacy of different radiotherapy schedules. This multi-institutional retrospective study included patients aged ≥65 years who underwent surgical resection followed by radiotherapy with or without temozolomide (TMZ) for newly diagnosed eGBM. Based on the significant factors identified in the multivariate analysis for overall survival (OS), the molecular GPA for eGBM (eGBM-molGPA) was established. A total of 334 and 239 patients who underwent conventionally fractionated radiotherapy (CFRT) and hypofractionated radiotherapy (HFRT) were included, respectively, with 86% of patients receiving TMZ-based chemoradiation. With a median follow-up of 17.4 months (range, 3.3-149.9), the median OS was 18.7 months for CFRT+TMZ group, 15.1 months for HFRT+TMZ group, and 10.4 months for radiotherapy alone group (CFRT+TMZ vs. HFRT+TMZ: HR 1.52, p<0.001; CFRT+TMZ vs. radiotherapy alone: HR 2.52, p<0.001). In a combined analysis with the NOA-08 and NORDIC trials, CFRT+TMZ group exhibited the highest survival rates among all treatment groups. The eGBM-molGPA, which integrated four clinical and three molecular parameters, stratified patients into low-, intermediate-, and high-risk groups. CFRT+TMZ significantly improved OS compared to HFRT+TMZ or radiotherapy alone in the low-risk (p=0.023) and intermediate-risk groups (p<0.001). However, in the high-risk group, there was no significant difference in OS between treatment options (p=0.770). CFRT+TMZ may be more effective than HFRT+TMZ or radiotherapy alone for selected eGBM patients. The novel eGBM-molGPA model can guide treatment selection for this patient population.

Algorithm-based Management of Infantile Hemangiomas: Reducing Sequelae and Surgical Interventions

Background: In Japan, oral propranolol (PPL) and pulsed dye laser are available for infantile hemangioma (IH) treatment without patient cost-sharing. However, no standardized algorithm exists to guide treatment selection that balances efficacy, potential side effects, and aesthetic risks. This study presents a comprehensive approach utilizing a treatment algorithm and aesthetic risk scoring system. Methods: This retrospective study analyzed outcomes from 156 patients with IHs. Oral PPL was used in IH patients with functional issues, whereas the rest underwent an aesthetic risk assessment that categorized them into low-, moderate-, or high-risk groups to guide treatment choices. Final treatment decisions depended on parental preference. The outcomes of algorithm-compliant and noncompliant patients were compared statistically. Results: The risk score's interrater reliability was 0.973 (95% confidence interval 0.933–0.992), with a mean intrarater reliability of 0.968 ± 0.027 and a mean evaluation time of 14.1 ± 5.0 seconds per case. Among the 156 patients, 88% pursued the algorithm-recommended treatment, whereas 12% opted for different approaches. Algorithm-compliant patients experienced significantly fewer sequelae than did noncompliant patients (5% versus 33%, P &lt; 0.001). Compared with noncompliant patients, algorithm-compliant patients tended to require shorter treatment durations (17.9 versus 25.4 mo, P = 0.08) and fewer laser sessions (5.8 versus 7.2, P = 0.30), with a younger age at resolution (21.3 versus 29.0 mo, P = 0.08). Conclusions: Aesthetic concerns can be crucial for patients with IHs. This study introduces a comprehensive IH management algorithm to reduce the sequelae requiring surgical interventions and improve patients’ quality of life.

Modeling Metformin and Dapagliflozin Pharmacokinetics in Chronic Kidney Disease.

Chronic kidney disease (CKD) is a complication of diabetes that affects circulating drug concentrations and elimination of drugs from the body. Multiple drugs may be prescribed for treatment of diabetes and co-morbidities, and CKD complicates the pharmacotherapy selection and dosing regimen. Characterizing variations in renal drug clearance using models requires large clinical datasets that are costly and time-consuming to collect. We propose a flexible approach to incorporate impaired renal clearance in pharmacokinetic (PK) models using descriptive statistics and secondary data with mechanistic models and PK first principles. Probability density functions were generated for various drug clearance mechanisms based on the degree of renal impairment and used to estimate the total clearance starting from glomerular filtration for metformin (MET) and dapagliflozin (DAPA). These estimates were integrated with PK models of MET and DAPA for simulations. MET renal clearance decreased proportionally with a reduction in estimated glomerular filtration rate (eGFR) and estimated net tubular transport rates. DAPA total clearance varied little with renal impairment and decreased proportionally to reported non-renal clearance rates. Net tubular transport rates were negative to partially account for low renal clearance compared with eGFR. The estimated clearance values and trends were consistent with MET and DAPA PK characteristics in the literature. Dose adjustment based on reduced clearance levels estimated correspondingly lower doses for MET and DAPA while maintaining desired dose exposure. Estimation of drug clearance rates using descriptive statistics and secondary data with mechanistic models and PK first principles improves modeling of CKD in diabetes and can guide treatment selection.

Serum Androgens as Predictive Biomarkers: Results From a Randomized Clinical Trial Comparing Enzalutamide and Abiraterone Acetate in Men With Metastatic Castration-Resistant Prostate Cancer

IntroductionThe purpose of this study was to investigate the association between baseline androgen concentrations and outcomes in men with metastatic castration-resistant prostate cancer (mCRPC) treated with first-line enzalutamide or abiraterone acetate plus prednisone (AAP). Materials and MethodsWe previously randomized men with mCRPC to enzalutamide or AAP to compare side-effects and measured androgen concentrations. In this post-hoc analysis, patients were grouped in quartiles (Q) based on their serum androgen values. Kaplan-Meier and Cox regression were used to analyze progression-free and overall survival for baseline androgen groups, treatment subgroups and their interaction. The trial was registered at clinicaltrialsregister.eu (2017-000099-27). ResultsEighty-four patients received enzalutamide and 85 AAP. Overall, higher (Q4) compared with lower (Q1) baseline serum testosterone was associated with longer progression-free survival (24.8 vs. 10.7 months, hazard ratio [HR] 0.52, 95% confidence interval [CI] 0.33; 0.84) and overall survival (52.8 vs. 31.5 months, HR 0.49, 95% CI 0.28; 0.85). The risk reduction in death seemed to be treatment dependent (treatment subgroup interaction P = .04). For men in the AAP subgroup, the Q4 compared with Q1 group had a significant lower risk of death (HR 0.30, 95% CI 0.13; 0.73), while no difference was found for enzalutamide (HR 0.77, 95% CI 0.35; 1.69). Similar results were found for the other androgens. ConclusionPre-treatment serum testosterone levels may be a clinically useful biomarker for predicting mCRPC treatment responses and guiding treatment selection.

Clinical and sociodemographic features of the Texas resilience against depression (T-RAD) study: Findings from the initial cohort

ObjectiveThe burden of major depressive disorder is compounded by a limited understanding of its risk factors, the limited efficacy of treatments, and the lack of precision approaches to guide treatment selection. The Texas Resilience Against Depression (T-RAD) study was designed to explore the etiology of depression by collecting comprehensive socio-demographic, clinical, behavioral, neurophysiological/neuroimaging, and biological data from depressed individuals (D2K) and youth at risk for depression (RAD). MethodsThis report details the baseline sociodemographic, clinical, and functional features from the initial cohort (D2K N = 1040, RAD N = 365). ResultsOf the total T-RAD sample, n = 1078 (76.73 %) attended ≥2 in-person visits, and n = 845 (60.14 %) attended ≥4 in-person visits. Most D2K (84.82 %) had a primary diagnosis of any depressive disorder, with a bipolar disorder diagnosis being prevalent (13.49 %). RAD participants (75.89 %) did not have a psychiatric diagnosis, but other non-depressive diagnoses were present. D2K participants had 9-item Patient Health Questionnaire scores at or near the moderate range (10.58 ± 6.42 > 24 yrs.; 9.73 ± 6.12 10–24 yrs). RAD participants were in the non-depressed range (2.19 ± 2.65). While the age ranges in D2K and RAD differ, the potential to conduct analyses that compare at-risk and depressed youth is a strength of the study. The opportunity to examine the trajectory of depressive symptoms in the D2K cohort over the lifespan is unique. LimitationsAs a longitudinal study, missing data were common. ConclusionT-RAD will allow data to be collected from multiple modalities on a clinically well-characterized sample. These data will drive important discoveries on diagnosis, treatment, and prevention of depression.

Anterior choroidal artery aneurysms: a systematic review and meta-analysis of outcomes and ischemic complications following surgical and endovascular treatment.

Anterior choroidal artery (AChA) aneurysms account for 2%-5% of all intracranial aneurysms. Treatment considerations include microsurgical clipping, flow diversion, or coiling with or without adjunctive devices. AChA aneurysms pose challenges in treatment due to the origination of the aneurysm from the origin or proximal segment of the AChA. The AChA is particularly susceptible to vasospasm and occlusion during treatment with devastating neurological deficits, including hemiparesis, hemianesthesia, lethargy, neglect, and hemianopia. In this study, the authors performed a meta-analysis to quantify the outcomes and complication rates across treatment modalities for AChA aneurysms and to identify risk factors reported in the literature. The authors performed a systematic review of AChA aneurysms treated with surgical clipping, endovascular coiling, or flow diversion and reported in the PubMed, Embase, Scopus, and Cochrane search databases. Single-arm meta-analyses of the selected outcomes were performed in RStudio. Literature review yielded 25 studies that met the inclusion criteria. In total, 1627 patients were included in the analysis, with 554 males, 1009 females, and 64 unspecified. The rate of any complication in the full cohort was 11.6%, with a rate of ischemic complications of 5.5% and a favorable recovery rate of 90.3% of all patients treated. In total, 1064 patients underwent surgical clipping, 443 were treated with coiling, and 120 patients with flow diversion. In clipped patients, the rate of total surgical complications was 17.6%, with an ischemic complication rate of 9.4%. The rate of good functional recovery, defined on the basis of a Glasgow Outcome Scale score of 4-5 or modified Rankin Scale score of 0-2, was 88.0%, and complete obliteration was achieved in 84.5% of surgically clipped aneurysms. The complication rate in coiled patients was 10.3%, with an ischemic complication rate of 3.0%. Good functional recovery was achieved in 88.6% of coiled patients and complete aneurysm obliteration in 74.1%. Flow diversion resulted in a complication rate of 1.3%, with 0.7% rate of ischemic complications. Good functional recovery was achieved in 98.4% of patients and complete aneurysm obliteration in 79.0% in the flow diversion group. Aneurysm morphological features that impacted the complication rate were also identified to augment quantitative data and to help guide treatment selection for AChA aneurysms. Flow diversion showed significantly lower total and ischemic complications and improved outcomes compared to clipping and coiling. There may be differences in outcomes between treatment types, especially when considering the varied patient presentations that guide treatment selection.

Prescription Medications and Overall Survival in Metastatic Hormone Sensitive Prostate Cancer.

With new therapies for metastatic prostate cancer, patients are living longer, increasing the need for better understanding of the impact of comorbid disease. Prescription medications may risk-stratify patients independent of established methods, such as the Charlson Comorbidity Index (CCI) and guide treatment selection. In a nationwide retrospective study of US Veterans, we used multivariable logistic regression and Cox proportional hazard modeling to evaluate the association between number and class of prescription medications and overall survival (OS) with age, race, body-mass index, prostate specific antigen (PSA), and Charlson comorbidities as covariates in veterans treated for de novo metastatic hormone sensitive prostate cancer (mHSPC) between 2010-2021. Among 8,434 Veterans, a median of nine medications and five medication classes were filled in the year prior to initial treatment with abiraterone or enzalutamide for mHSPC. Veterans on 1-4 medications had an average survival of 38 months compared to 5-9 medicines (33 months), 10-14 medicines (27 months), and 15+ medicines (22 months) (p<0.001). After adjusting for age, race, body mass index (BMI), PSA, CCI, and year of diagnosis, both the number of medications and medication classes were associated with increased mortality. The adjusted hazard ratio (aHR) [95% confidence interval (CI)] was 1.03 (1.02-1.03) for the number of medications and 1.05 (1.04-1.07) for medication classes. Medications within ATC B (blood/blood forming organs), ATC C (cardiovascular), and ATC N (nervous) were associated with worse OS, with aHRs of 1.14 (1.07, 1.21), 1.14 (1.06, 1.22), and 1.12 (1.06, 1.19), respectively. The number and class of medications were independently associated with overall survival in patients undergoing treatment for mHSPC. With new therapies for advanced prostate cancer, patients are living longer, highlighting the need for a better understanding of the impact of comorbid diseases. Simple methods to assess disease burden and prognosticate survival have the potential to guide treatment decisions.

Spatial tumor immune microenvironment phenotypes in ovarian cancer

Immunotherapy has largely failed in ovarian carcinoma (OC), likely due to that the vast tumor heterogeneity and variation in immune response have hampered clinical trial outcomes. Tumor-immune microenvironment (TIME) profiling may aid in stratification of OC tumors for guiding treatment selection. Here, we used Digital Spatial Profiling combined with image analysis to characterize regions of spatially distinct TIME phenotypes in OC to assess whether immune infiltration pattern can predict presence of immuno-oncology targets. Tumors with diffuse immune infiltration and increased tumor-immune spatial interactions had higher presence of IDO1, PD-L1, PD-1 and Tim-3, while focal immune niches had more CD163 macrophages and a preliminary worse outcome. Immune exclusion was associated with presence of Tregs and Fibronectin. High-grade serous OC showed an overall stronger immune response and presence of multiple targetable checkpoints. Low-grade serous OC was associated with diffuse infiltration and a high expression of STING, while endometrioid OC had higher presence of CTLA-4. Mucinous and clear cell OC were dominated by focal immune clusters and immune-excluded regions, with mucinous tumors displaying T-cell rich immune niches.

Letter to the Editor Regarding: “Redefining the Classification for Bertolotti Syndrome: Anatomical Findings in Lumbosacral Transitional Vertebrae Guide Treatment Selection”

Letter to the Editor Regarding: “Redefining the Classification for Bertolotti Syndrome: Anatomical Findings in Lumbosacral Transitional Vertebrae Guide Treatment Selection”