Amid the rising burden of cancer in Europe, participation in colorectal, breast, and cervical cancer screening programmes remains inadequate. The potential role of social support in increasing screening uptake across different types of cancer screening and within multinational contexts remains underexplored. Two-level multilevel analyses were conducted using data from the European Health Interview Survey Wave 3 in 18 European countries. We analysed data from subsamples of participants who responded to the questions for colorectal (n = 65,089), breast (n = 35,281), and cervical (n = 36,763) cancer screening. Social support was measured using the Oslo-3 Social Support Scale. Participants were classified as overdue for screening according to cancer-specific guidelines for different target age groups. The overall prevalence of being overdue was 43% for colorectal, 31% for breast, and 19% for cervical tests; however, substantial variation was observed between countries (i.e., from 22% in Denmark to 72% in Greece for colorectal, 4% in Sweden to 57% in Estonia for breast, and 6% in Sweden to 43% in the Netherlands for cervical screenings). Stronger social support was associated with a greater likelihood of being up to date with cancer screening, with stronger associations observed for breast and cervical cancers than for colorectal cancer. Country-level factors, including screening programme availability, social progress, out-of-pocket payments, and general practitioner density, explained nearly half of the variation in breast and colorectal cancer screening uptake, but less so for cervical cancer. Interventions promoting screening uptake should consider strengthening individual-level social support and addressing contextual-level structural barriers.
We assessed the feasibility of implementation, reduction in magnetic resonance imaging (MRI) use, and cost implications of integrating Stockholm3 as a reflex blood test in organized prostate cancer testing (OPT). This pragmatic, population-based implementation study included men aged 50-52 yr invited to OPT in 2023 (n = 17 801) and 2024 (n = 30 556) in Health Region Stockholm-Gotland. The experimental group (2024) had a Stockholm3 test if prostate-specific antigen (PSA) ≥2 ng/ml and an MRI if Stockholm3 ≥15%. The control group (2023) followed standard OPT (MRI if PSA ≥3 ng/ml). Outcomes were MRI use (primary), biopsies performed, detection of Grade Group (GG) 1 and GG ≥2 cancer, and Stockholm3 cost thresholds. Relative proportions (RPs) and decision-tree cost modeling were used. MRI use decreased by 64%, from 2.7% (181/6663) in 2023 to 1.0% (70/7070) in 2024 (RP 0.36; 95% confidence intervals [CI], 0.28-0.48); biopsy rates decreased from 0.6% to 0.4% (RP 0.67; 95% CI, 0.41-1.07). Detection of GG 1 cancer decreased from 0.17% (11/6663) to 0.08% (6/7070) (RP 0.51; 95% CI, 0.19-1.39), and detection of GG ≥2 cancer decreased from 0.20% (13/6663) to 0.14% (10/7070) (RP 0.72; 95% CI, 0.32-1.65). A cost of €92 per Stockholm3 test would achieve cost neutrality. Limiting Stockholm3 testing to men with PSA ≥3 ng/ml would reduce MRI use and costs. Study limitations include the nonrandomized design, few cancer events, restricted age range, and short follow-up. Integrating Stockholm3 as a reflex test in the first round of an OPT program is feasible. Reflex testing at PSA ≥2 ng/ml and PSA ≥3 ng/ml was associated with reductions in the numbers of MRI scans and biopsies performed. No cancers were detected at PSA 2.0-2.9 ng/ml; however, the study was underpowered to assess cancer detection, and this finding should be considered hypothesis-generating.
Folic acid (FA)-modified gadolinium nanoparticles are promising candidates for magnetic resonance imaging (MRI) contrast agents due to their high cancer specificity. Therefore, this study aims to modify nanoparticles with polyethylene glycol (PEG)-FA to enhance their biocompatibility and specificity toward cervical cancer target via folate receptor (FR)-mediated endocytosis. Spherical nanoparticles less than 20 nm were characterized by dynamic light scattering and transmission electron microscopy, with UV absorbance peaks at 282 and 362 nm confirming the successful attachment of FA. Additionally, the zeta potential at - 51.23 mV indicated good colloidal stability. Subsequently, an in vitro investigation was performed using three different FA-expressing cancer cell lines: HEK-293 (-), HeLa ( +), and KB (+ +), demonstrating that the cancer cells remained > 90% viable after 24 h incubation with the nanoparticles. There was enhanced FA-nanoparticle uptake in HeLa and KB, with minimal uptake in HEK-293 cells. In addition, FA pretreatment reduced uptake, confirming the receptor specificity. Compared to nanoparticles without modification, modified nanoparticles showed a significant increase in uptake in cancer cells expressing the FA receptor (p < 0.0001). These results support the potential of FA-modified gadolinium nanoparticles as a receptor-targeted contrast agent for further cervical cancer MR imaging applications.
Bladder cancer is the 11th most common cancer in the United Kingdom, with approximately 10,500 new cases annually. Diagnosis and surveillance typically involve cystoscopy, an expensive, time-consuming, and uncomfortable procedure which has encouraged efforts to identify biomarkers, particularly in urine, given its direct contact with malignant tissue. Urine collected from 100 participants (50 bladder cancer patients, 50 controls) was subjected to solvent extraction followed by gas chromatography-mass spectrometry (GC-MS) to determine potential volatile and semi-volatile biomarkers. The results were analysed using classical univariate statistics and machine learning methods. Five machine learning algorithms were evaluated, with recursive feature elimination (RFE) identifying optimal biomarker panels. Machine learning with XGBoost achieved area under the receiver operating characteristic curve (AUROC) of 0.869 (95% CI: 0.740-0.988), representing a significant improvement over the classical statistical approach (AUROC 0.752). An 8-metabolite panel achieved balanced sensitivity and specificity of 85%, or 95% sensitivity with 70% specificity when optimised for screening. The findings indicate that solvent extraction of urine shows promise for isolating putative biomarkers of bladder cancer. Employing machine learning achieved diagnostic accuracy potentially suitable for clinical deployment as a non-invasive bladder cancer detection tool.
Adiposity increases the risk of post-menopausal oestrogen receptor (ER)-positive breast cancer. Inflammation, insulin, and insulin-like growth factors and sex-steroid hormones may explain this effect. We performed interventional mediation analysis to estimate the effects of hypothetical interventions targeting these pathways in females with obesity on reducing their excess risk of post-menopausal ER-positive breast cancer relative to females with normal weight. The mediation analysis included 1260 post-menopausal females (352 with ER-positive breast cancer) from a case-cohort within the Melbourne Collaborative Cohort Study. A Monte Carlo g-computation approach with non-parametric bootstrapping was used to estimate the risk differences (RDs) and 95% confidence intervals (CIs) for interventional direct and indirect effects of hypothetical interventions that shift the joint distribution of inflammation, insulin, and sex-steroid hormone biomarkers in females with obesity to the levels observed in females with normal weight. The estimated RD for the total effect of obesity relative to normal weight on post-menopausal ER-positive breast cancer was 16.1 (95% CI: 3.3, 30.4) per 1000 females. The RDs for indirect effects through inflammation, insulin, and sex-steroid hormones were 16.4 (95% CI: 4.3, 27.2), -8.4 (95% CI: -23.4, 1.2), and 13.0 (95% CI: 3.3, 23.7) per 1000 females, respectively. The - RD for the direct effect not via any of these three pathways was -5.3 (95% CI: -17.4, 10.6) per 1000 females. Inflammation and sex-steroid hormones, but not insulin, contributed to the detrimental effect of adiposity on the risk of post-menopausal ER-positive breast cancer. Interventions targeting these pathways may reduce the risk for females with obesity.
Smokers are eligible for lung cancer screening using low dose CT (LDCT) if they have a sufficiently high risk of lung cancer. In England, for example, people are eligible if their estimated risk using either of two validated models (PLCOm2012 and Liverpool Lung Project) exceeds a certain threshold. Risk is often estimated using only cigarette consumption (duration and number per day), yet many smokers also use other cancer-causing tobacco products. SUMMIT is a prospective cohort study of a LDCT screening service. We evaluated the impact of cigars, pipes, and cigarillos on lung cancer risk. Among 13,000 participants who were current/former cigarette smokers, 511 (1 in 25) were also regular users of cigars, pipes, or cigarillos. The 5-year cumulative lung cancer incidence in people who currently smoked both types of tobacco products was 8.85%, versus 5.74% for cigarette only current smokers. Among these 511 participants, the percentage whose risk was below the screening eligibility threshold ignoring other tobacco products which then exceeded the threshold including these products was 0.6% using LLPv2, and 8.2% using PLCOm2012. All tobacco consumption should be considered when determining screening eligibility to avoid missing those who can benefit from LDCT. Clinicaltrials.gov no: NCT03934866.
Prostate cancer represents the third leading cause of cancer-related mortality in the male population. Androgen deprivation therapy efficacy has been significantly enhanced by the addition of docetaxel chemotherapy and androgen receptor pathway inhibitors (ARPI), such as abiraterone, enzalutamide, apalutamide, and darolutamide. These agents have demonstrated improvements in both overall survival (OS) and progression-free survival (PFS). Nevertheless, a subset of patients eventually progresses to metastatic castration-resistant prostate cancer (mCRPC). The prostate-specific antigen (PSA) nadir, defined as the lowest PSA level achieved during therapy, has emerged as an early surrogate marker of treatment response and favorable prognosis. We conducted a meta-analysis to elucidate the prognostic value of the depth of PSA response in patients with metastatic metastatic hormone-sensitive prostate cancer (mHSPC) treated with ARPI or docetaxel. This is a reconstructed individual patient data (IPD) meta-analysis, in which prospective and retrospective clinical trials concerning patients with mHSPC who received first-line therapy with an ARPI or docetaxel were included. Prospective or retrospective studies on mHSPC patients with available data on the lowest value of PSA reached were included. IPD from the Kaplan-Meier curves of enrolled studies were obtained with the software IPDfromKM. Primary endpoints of the analysis were overall survival (OS) and progression-free survival (PFS) in patients who reached a PSA nadir ≤ 0.2 versus PSA nadir > 0.2. A total of 8 reports from 8 studies were included, collecting data from 1638 patients for the OS analysis and 1104 for the PFS analysis. In terms of median PFS (mPFS), the PSA nadir ≤ 0.2 arm had an advantage: mPFS not reached (NR) versus 12.1 months HR 0.19 (95% CI 0.16-0.23, p < 0.0001). In terms of median OS (mOS) the PSA nadir ≤ 0.2 arm had an advantage compared with the PSA nadir > 0.2: mOS 92.8 months versus 34 months (HR 0.27, 95% CI 0.22-0.33, p < 0.0001). This meta-analysis confirms the prognostic value of PSA nadir in patients with mHSPC treated with docetaxel or ARPIs. Achieving a PSA nadir ≤ 0.2 ng/mL was significantly associated with improved OS and PFS, highlighting its relevance as an early marker of treatment efficacy.
Cancer cells frequently show elevated glucose consumption to support proliferation and survival. This led to the assumption that glycolytic inhibitors could be effective in cancer treatment. However, barriers to clinical implementation remain. Adaptive strategies, such as metabolizing alternative nutrients, may play a role. Here, we investigated the use of an understudied sugar, mannose, in lung cancer cells and xenografts. Stable isotope tracing reveals enhanced contribution of mannose to GDP-mannose and GDP-fucose, key glycosylation precursors, upon treatment with the glycolytic inhibitor 2-deoxyglucose (2-DG) or glucose starvation in vitro. Mannose restores the glucose-withdrawal-induced decrease of GDP-mannose and GDP-fucose pools, and partially rescues proliferation upon 2-DG treatment or glucose deprivation. 13C6-mannose infusion in patient-derived xenograft mice reveals a considerable contribution of mannose to GDP-mannose and GDP-fucose in tumors, which is further enhanced by 2-DG. In normal lungs, the pathway is only partially active. Mannose is also shuttled towards glycolysis in lung tumors in vivo and glucose-deprived cells in vitro. In conclusion, mannose utilization for glycosylation precursor synthesis represents an adaptive strategy in lung cancer cells under metabolic stress.
Cancer patients commonly experience declines in quality of life and physical function. The Eastern Cooperative Oncology Group (ECOG) Performance Status Scale is widely used to assess functional status; however, it lacks objective measures of physical fitness. The Senior Fitness Test (SFT) provides a structured and standardized approach to objectively quantify functional abilities. This study aimed to assess functional status in cancer patients using the SFT and to examine its relationship with ECOG performance status. Patients undergoing or having completed anti-cancer treatment were recruited for this study. Multicomponent functional fitness was assessed by a trained exercise scientist using the Senior Fitness Test (SFT), including the 2-min step test, 30-s arm curl, 30-s chair stand, chair sit-and-reach, back scratch and the Timed Up-and-Go Test (TUGT). ECOG performance status was extracted from current medical records or determined by a senior researcher according to official rating guidelines. For each SFT component, individual test results were assigned an age based on normative reference values. Fitness age (FA) was calculated as the mean age across all six SFT measures. A total of n = 30 subjects (f = 15, 61.6 ± 12.1y, 16 during & 14 after therapy) participated in this study. Within the present sample, FA differed significantly from chronological age (+ 8.59 years, 95%-CI: 3.65-13.5, p<0.001) with no differences between therapy stages. Patients defined as limited in their functional status (ECOG 1&2) showed no significant difference between FA and chronological age compared to patients with ECOG stage 0 (p=0.346). The Senior Fitness Test (SFT) is a feasible tool to assess functional status in cancer patients and survivors. Participants exhibited functional deficits equivalent to nearly nine years of age advancement compared with healthy norms, which were not reflected by ECOG performance status and did not differ between patients undergoing treatment and survivors. These findings emphasize the need for objective functional assessments to guide tailored exercise interventions that address long-term limitations and improve quality of life.
Although thyroid cancer has a favorable prognosis, patients experience significant psychological distress from the time of diagnosis. The study aimed to investigate the distress level in patients diagnosed or suspected of thyroid cancer, to characterize the major sources, and to determine the independent predictors of distress. In this prospective study, patients who had presented to our institution between January 2024 and June 2025 were asked to complete the online questionnaires including the Distress Thermometer (DT) with problem list (PL). Group comparisons between the distress and non-distress groups were performed using Chi-square and t tests. Binary logistic regression analysis was used to identify independent factors associated with distress. A total of 649 patients were included in analysis. 524 (80.74%) patients were classified in the distress group, while 125 (19.26%) were divided into the non-distress group. The mean DT scores were 7.21 ± 1.91 and 1.40 ± 1.24, respectively. The most frequently reported problems were worry (552, 85.05%), nervousness (498, 76.73%), sadness (433, 66.72%), treatment decisions (414, 63.79%), and fears (404, 62.25%). In multivariable analysis, male sex was independently associated with higher distress, whereas older age, higher education level, and stable employment were associated with lower odds of distress. Practical and emotional problems significantly predicted distress. Clinically significant distress is highly prevalent at the time of thyroid cancer diagnosis. DT with PL is an efficient screening instrument and could be easily incorporated into practice. Early identification and support for vulnerable patients may help alleviate psychological burden and improve overall care.
Exercise is recognized for its efficacy in alleviating cancer-related fatigue (CRF). However, the effect of high-frequency exercise on CRF has not been clarified. This study aimed to elucidate the association between exercise frequency during hospitalization and CRF in patients with lymphoma. This retrospective study included patients with lymphoma admitted for chemotherapy who were advised to engage in aerobic and resistance training once daily, six days per week. Exercise frequency was calculated as the percentage of hospitalization days during which therapy was administered. Participants were categorized into two groups based on exercise frequency. CRF was evaluated using the Cancer Fatigue Scale (CFS), comprising 15 items that assess physical, affective, and cognitive factors. A total of 130 patients (median age: 72 [range: 66 -78] years) were eligible to participate. The median frequency of exercise was 71.4%. Multiple regression analysis revealed that the exercise frequency significantly affected the physical CFS score at discharge. However, no statistically significant relationship was observed between exercise participation frequency and other CFS scores. Higher-frequency exercise was significantly associated with a reduction in CRF at discharge.
Biliary tract cancer (BTC) has a high postoperative recurrence rate and limiting long-term survival. Accurate prediction of recurrence is vital for clinical management. Carbohydrate antigen 19-9 (CA19-9) and the neutrophil percentage-to-albumin ratio (NPAR) are established prognostic markers in various cancers, but their combined value in BTC remains unclear. This study assessed the predictive role of the combination of CA19-9 and NPAR on time to recurrence (TTR) and introduced the novel NPAR-CA19-9 stratified score (NCSS). A total of 145 BTC patients who underwent resection between March 2019 and December 2023 were analyzed. Preoperative blood samples, collected within two weeks of surgery, were used to measure CA19-9 and NPAR. Cutoff values were defined using the Maximum Selected Rank Statistic (MSRS). NCSS (0-2) were assigned according to marker levels and evaluated using Kaplan-Meier survival analysis and Cox regression models. Higher NCSS were associated with shorter TTR and reduced overall survival (P < 0.001). Cox regression confirmed NCSS as an independent predictor of recurrence [NCSS = 1: hazard ratio (HR) = 1.82, 95% confidence interval (CI): 1.05-3.14; NCSS = 2: HR = 2.95, 95% CI: 1.54-5.64] and overall survival (NCSS = 1: HR = 5.21, 95% CI: 1.19-22.82; NCSS = 2: HR = 11.88, 95% CI: 2.44-57.75). Subgroup analysis showed that patients with NCSS = 1 or 2 benefited from adjuvant chemotherapy, whereas those with NCSS = 0 did not. Incorporating NCSS into a nomogram improved prediction of TTR compared with a model excluding NCSS (C-index: 0.72 vs. 0.70; P = 0.027). NCSS is a novel, simple, and effective preoperative scoring system that predicts TTR and overall survival in BTC patients, supporting more individualized treatment planning.
The incidence of pancreatic ductal adenocarcinoma (PDAC) is increasing but clinical outcomes remain poor and new treatments are required. IGF2BP3 is an oncofetal m6A-reading RNA regulatory protein whose expression is commonly observed in PDAC and which may represent an important therapeutic target. IGF2BP3 protein is expressed in >95% of primary tumours whilst RNA expression ranges from 3 to 3000-fold above normal epithelium. siRNA knockdown reveals IGF2BP3 to strongly support expression of gene programs related to DNA replication, cell cycle and apoptosis, TNF signalling and epithelial-mesenchymal transition. Direct sequencing of native RNA further reveals IGF2BP3-mediated enhancement of 863 RNA isoforms with suppression of 389 isoforms. m6A, m5C and pseudouridine (ψ) RNA modifications were seen in 97% of transcripts within the PDAC transcriptome and enriched within MYC gene targets. IGF2BP3 regulated the pattern of RNA modification with a substantial impact on m5C modifications of miRNA and scRNA, and genes associated with regulation of TNF signalling. Knockdown of IGF2BP3 expression in primary tumour organoid cultures suppressed proliferation and elicited apoptosis, indicating a critical requirement for IGF2BP3 within malignant stem cells. These data show that IGF2BP3 is expressed consistently in PDAC, plays a dominant role in regulation of RNA splicing and modification, and supports cancer stem cell proliferation and survival. IGF2BP3 therefore occupies a critical position within the RNA regulon of PDAC and represents an important therapeutic target in this tumour of unmet need.
Aspartyl-tRNA synthetase 2 (DARS2), the mitochondrial enzyme responsible for aminoacylation of aspartyl-tRNA, is traditionally known for its effect on protein synthesis. Recently, DARS2 is reported to be implicated in tumorigenesis. However, its specific effect on breast cancer (BC) is poorly understood. The present work employed bioinformatics tools for analyzing DARS2 expression among BC patients and its association with clinicopathological characteristics and patient prognosis. We evaluated DARS2 expression within BC cells and tissues and assessed how DARS2 knockdown or PI3K pathway activation affected cell growth, migration, invasion, apoptosis, as well as cell cycle progression. Mechanistically, we analyzed how DARS2 regulated the PI3K/Akt/GSK-3β/β-catenin pathway. Additionally, a xenograft tumor model was constructed to validate our in vitro findings. According to our observations, DARS2 expression significantly increased in BC cells and tissues. Knockdown of DARS2 markedly suppressed cell growth, invasion, migration, and epithelial-mesenchymal transition (EMT), but enhanced their apoptosis. Mechanistic studies revealed that DARS2 knockdown suppressed the PI3K/Akt/GSK-3β/β-catenin pathway, whereas PI3K pathway activation with 740Y-P reversed the impacts of DARS2 knockdown. In vivo experimental results further verified that DARS2 suppression significantly suppressed tumor growth and metastasis through downregulating the PI3K/Akt/GSK-3β/β-catenin pathway. Collectively, these results indicate that DARS2 promotes the growth, migration, invasion, and EMT of BC cells by regulating the PI3K/Akt/GSK-3β/β-catenin signaling pathway.
Artificial chemical synapses, which specifically identify, transmit, and process molecular information, find promising applications in precision medical diagnosis, neural-electronic interface, and in-memory computing. However, to implement biomarker-triggered neuronal excitability modulation with artificial iontronic devices remains a significant challenge. Herein, we demonstrate a capture DNA integrated angstrom-fluidic chemical synapse in which the intramembrane ionic conductance can be switched between excitatory and inhibitory states by specific DNA-target interactions on the outer membrane surface. Experimental results and theoretical calculations unveil that capture of specific biomarker results in a bidirectional space charge polarization, and establishes opposite local concentration gradient at the membrane surface. Driven by this reversible concentration gradient, cation influx or efflux modulate the number density of ionic charge carriers inside the membrane, analogy to the hyperpolarization and depolarization modes of biological chemical synapses. Using a convolutional neural network algorithm to process the ionic conductance enhancement and depletion signals, we develop a diagnostic approach for early prostate cancer with 100% accuracy for both retrospective analysis of 105 clinical specimens, and prospective double-blind trials (n = 10). This work sheds light on artificial chemical synapses based medical diagnosis, and provides a blueprint for neural-like iontronic network for chemical information processing.
This study quantified naturally occurring gamma-emitting radionuclides (226Ra, 232Th, 40K) in eight medicinal plants collected from the Senhaja Srair region of northern Morocco using HPGe gamma spectrometry. 40K activities ranged from 214.66 to 1060.34 Bq kg-1 (highest in the Lamiaceae family), whereas 226Ra (0.23-2.10 Bq kg-1) and 232Th (1.07-4.03 Bq kg-1) activities remained low. The estimated annual committed effective dose by ingestion ranged from 8.04 × 10-6 to 1.36 × 10-5 Sv y-1 for adults and from 1.23 × 10-5 to 6.29 × 10-5 Sv y-1 for children. The corresponding excess lifetime cancer risk (ELCR) reached a maximum value of 2.20 × 10-4. These results indicate that the investigated gamma-emitting radionuclides contribute only a limited fraction of the estimated ingestion dose and provide baseline data on natural gamma radioactivity in medicinal plants from northern Morocco.
We previously generated a global bulk-level proteogenomic atlas of metastatic colorectal cancer (CRC) in a Chinese cohort (CCRC). Using formalin-fixed paraffin-embedded tissues from this cohort, we identified 2095 ectopic lymphoid-like structures (ELSs) across 132 primary tumors. Both lymphoid aggregates (Aggs) and tertiary lymphoid structures (TLSs) were significantly associated with metastasis and clinical outcomes in CRC, in which the spatial and compositional heterogeneity of ELSs and their clinical relevance remain unknown. Here, we upgraded our LCM-MTA platform to version 2.0 for deep spatial proteomics and profiled spatial proteomic landscapes from matched mCRC and non-mCRC cases with comparable baseline clinical features. This analysis revealed pronounced spatial heterogeneity in protein expression, distinguishing ELSs from parenchymal regions in paired tumor and para-carcinoma tissues. Notably, TLSs displayed distinct functional states: mCRC-associated TLSs showed enrichment of anti-tumor immune activation pathways, whereas non-mCRC TLSs were enriched in acute inflammatory response pathways. Based on these findings, we developed a 13-protein TLS signature and scoring system to predict metastasis and prognosis in the CCRC cohort, validated in two independent CPTAC cohorts. We present a comprehensive spatial proteomic map of ELSs in metastatic CRC and identify a TLS-based signature with strong potential for predicting metastasis and clinical outcomes.
Detecting localized prostate cancer (PC) with metastatic potential-defined as unfavorable-histology PC (uhPC), comprising Grade Group (GG) ≥3 disease or GG 2 disease with cribriform/intraductal features-is critical for guiding appropriate intervention. We evaluated the utility of the Prostate Imaging Reporting and Data System (PI-RADS) and the automated Restriction Spectrum Imaging restriction score (RSIrs; a biophysics-based quantitative MRI biomarker) for uhPC detection and localization. We evaluated patient-level detection of uhPC in a multicenter cohort with biopsy as the reference standard and lesion-level localization in a separate cohort with whole-mount histopathology (WMHP) from radical prostatectomy. The area under the receiver operating characteristic curve (AUC) was calculated to compare patient-level detection of uhPC using PI-RADS and RSIrs. PI-RADS and RSIrs were used to evaluate sensitivity for the most aggressive tumor within the prostate (index tumor) and for all uhPC tumors on WMHP. The AUC for patient-level detection of uhPC did not differ significantly between PI-RADS and RSIrs in 1022 patients from five centers (p = 0.13). At the lesion level (n = 103 patients), sensitivity for the index tumor was 87% (95% confidence intervals [CI], 79-94) for PI-RADS, 85% (95% CI, 78-93) for RSIrs, and 93% (95% CI, 86-98) for the two combined. For all uhPC tumors, sensitivity was 81% (95% CI, 73-90) for PI-RADS, 86% (95% CI, 78-93) for RSIrs, and 90% (95% CI, 82-97) for the two combined. A limitation of the lesion-level analyses was that only patients who opted for surgery could be included. MRI showed high sensitivity for detecting uhPC, reinforcing its value for identifying biologically aggressive disease. Both PI-RADS and automated RSIrs may be useful for targeted biopsy and tumor-focused treatment, such as focal radiation dose escalation to aggressive intraprostatic lesions.
Small-cell lung cancer (SCLC) is widely considered one of the most aggressive human malignancies, characterized by development of rapid metastases and eventual resistance to platinum chemotherapy and immunotherapy. For decades, despite rigorous scientific investigation and well-established mouse models providing a basis for mechanistic understanding, there were limited therapeutic advances for SCLC. The past decade has seen reinvigoration of drug development for SCLC as well as US Food and Drug Administration (FDA) approval of tarlatamab, a bispecific T-cell engager with unprecedented survival advantage in this recalcitrant disease. Multiple other promising clinical trials in the first and later-line settings are underway that seek to challenge standards of first-line chemoimmunotherapy, investigate combination treatments in the later line, and introduce T-cell engagers earlier in treatment. This review provides a comprehensive primer on the biology and molecular landscape of SCLC, in the context of how both shape ongoing investigational strategies. A broad overview of established multidisciplinary management of both limited-stage and extensive-stage SCLC is discussed to provide understanding of how the next decade is likely to bring significant clinical gains as emerging therapeutics seek to redefine the management of SCLC and build upon novel advances.
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