Cancer Biopsies Research Articles

Lymphatic mapping in second primary or recurrent oral cavity cancer with prior neck treatment: A case series and scoping review

ObjectivesLymphatic mapping is an established technique to map drainage patterns in oral cancer. Its utility in patients who have undergone prior radiation or neck dissection is not well studied. MethodsPatients presenting to a single tertiary cancer center between 2021–2023 for a recurrent/second oral cancer that underwent lymphatic mapping were considered. All patients had a history of a head and neck cancer treated with either radiation or neck dissection. We further conducted a scoping review in MEDLINE, Embase, and Web of Science of lymphatic mapping in oral cancer patients with previous neck treatment. ResultsIn our single center review, a total of 11 patients were included. 73 % received prior radiotherapy and 55 % underwent prior neck dissections for a head and neck cancer. Lymphoscintigraphy-directed neck dissections identified sentinel nodes in 9/11 patients, with only one patient who had positive sentinel node disease. There were no reports of regional recurrence at a median of 10 months follow-up. Our scoping review of 980 studies identified 151 additional patients who underwent sentinel node biopsy for a second oral cancer after previous neck treatment. Overall, the negative predictive value of lymphatic mapping in all studies was 96.7 %. ConclusionLymphatic mapping is feasible in secondary or recurrent oral cavity cancers even in patients with prior radiation or surgical management of the neck. The literature to date demonstrates a negative predictive value of ∼ 97 % for sentinel node mapping and warrants further consideration in the management of salvage oral cancer.

Key issues in diagnostic accuracy of sentinel lymph node biopsy in early-stage ovarian cancer: systematic review and meta-analysis

ObjectiveSentinel lymph node (SLN) mapping may reduce the morbidity of lymphadenectomy while maintaining diagnostic accuracy. Nevertheless, SLN mapping in epithelial ovarian cancer is still under investigation. This systematic review and...

Diagnostic Accuracy of PSMA PET-Guided Prostate Biopsy in Prostate Cancer—A Systematic Review and Meta-analysis

Purpose Early diagnosis and treatment of prostate cancer (PC) are crucial for effective management and improved patient outcomes. Newer imaging modalities like prostate-specific membrane antigen PET have shown superior diagnostic performance in detecting PC and clinically significant PC (csPC). This systematic review and meta-analysis aims to synthesize evidence on the diagnostic performance of PSMA PET-guided prostate biopsy in detecting PC and csPC. Patients and Methods The study followed the PRISMA-DTA guidelines. Using a predefined search strategy, 3 databases (PubMed, Embase, and Web of Science) were systematically searched using appropriate keywords. A meta-analysis was conducted using diagnostic accuracy parameters of the included studies. Risk of bias assessment was done using the QUADAS-2 tool. Results Out of 378 articles, 20 were assessed for full-text screening and 10 articles with 874 patients were finally included. Eight studies reported a pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of 0.90 (95%confidence interval [CI], 0.82–0.95), 0.93 (95% CI, 0.57–0.99), 12.3 (95% CI, 1.5–98.9), 0.10 (95% CI, 0.05–0.20), and 117 (95% CI, 12–1178), respectively, for detecting PC using PSMA PET-guided prostate biopsy with an area under the summary receiver operating characteristics curve of 0.94 (95% CI, 0.92–0.96). Similarly, 6 studies reported a pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of 0.89 (95% CI, 0.82–0.94), 0.65 (95% CI, 0.49–0.79), 2.6 (95% CI, 1.6–4.1), 0.17 (95% CI, 0.09–0.31), and 15 (95% CI, 6–41), respectively, for detecting csPC using PSMA PET-guided prostate biopsy with area under summary receiver operating characteristics curve of 0.86 (95% CI, 0.82–0.88). Conclusions PSMA PET-guided prostate biopsy has a high diagnostic accuracy in detecting PC and csPC in patients with clinical suspicion of PC, and provides a 1-stop solution for early diagnosis and staging of PC.

Impact of skin biopsy practices: A comprehensive nationwide study on skin cancer and melanoma biopsies.

Due to a multitude of factors, skin cancer incidence is increasing and challenges medical professionals in biopsy decision-making. While skin cancer may have a profound impact on the patient and be costly for society, there is little knowledge about the number and cost of benign skin lesions biopsied as collateral damage. This study evaluates the number and costs of skin biopsies in Denmark over 15 years, focusing on benign and malignant skin lesions and melanomas across medical settings. It aims to determine the benign to malignant ratio (BMR) and number needed to biopsy (NNB) and estimate the direct cost of benign skin lesion biopsies in the Cancer Pathway from the perspective of a public healthcare system. The study included 4,481,207 biopsy specimens from January 2007 to June 2022 from the Danish Pathology Data Bank, of which 151,988 from the Cancer Pathway were included in the primary analysis of BMR. The national reimbursement rates for biopsies were used, alongside histopathological examination costs extracted from several pathology departments, for a Monte-Carlo simulation of a simple cost and sensitivity analysis. The number of biopsies increased by 39.1% from 2007 to 2021. Overall BMR for malignancy was 4.1:1, and NNB for melanoma was 31.8, but biopsies performed on clinical suspicion of malignancy or melanoma had a BMR and NNB of 1.5:1 and 2.8, respectively. The cost of benign skin biopsies performed on suspicion of cancer or melanoma in 2021 was €6.6M, predominantly in hospitals. A healthcare system that employs filtering functions before biopsy of skin lesions can achieve some of the lowest BMR reported in the world, but with most benign skin lesion excisions due to suspicion of malignancy performed in the expensive hospital setting. Including clinical reason for biopsy in diagnostic accuracy studies using NNB is crucial.

Role of bone scan for investigation of breast cancer and its applicability in future management.

Objective: To find out the usefulness of bone scan in all stages of breast cancer. Study Design: Prospective Observation Study. Setting: Surgical Unit I & III Ghulam Muhammad Mahar Medical College Hospital, Sukkur. Period: October 2020 till September 2022. Methods: A total of 300 patients were selected who were newly diagnosed with breast cancer (Biopsy Proven). Data was collected for all these patients which included age, risk factors for breast cancer, findings on local examination, histopathology findings, stage of the cancer and result of the bone scan. Results: In our study, 78% patients were in 4th and 5th decade of life with mean age of 53.46±7.66 years. ‘Age above 40’ was the commonest risk factor for breast cancer followed by positive family history for breast cancer. Tumor size ranged from 2 to 13.2 cm with mean size of 6.06±1.92 cm. In our study, most common type of carcinoma was invasive ductal carcinoma (71.3%) followed by invasive lobar carcinoma (50%). Only 32 (10.67%) out of 300 patients had positive bone scan. Majority of the bone scan positive cases belonged to the Stage IIIB, IIIC and IV. Conclusion: It is concluded in our study that routine use of bone scan in cases of stage 1 and 2 breast cancer is not recommended; only stage 3A or advances cases should undergo bone scan.

Quantitative proteomic mass spectrometry of protein kinases to determine dynamic heterogeneity of the human kinome.

The kinome is a dynamic system of kinases regulating signaling networks in cells and dysfunction of protein kinases contributes to many diseases. Regulation of the protein expression of kinases alters cellular responses to environmental changes and perturbations. We configured a library of 672 proteotypic peptides to quantify >300 kinases in a single LC-MS experiment using ten micrograms protein from human tissues including biopsies. This enables absolute quantitation of kinase protein abundance at attomole-femtomole expression levels, requiring no kinase enrichment and less than ten micrograms of starting protein from flash-frozen and formalin fixed paraffin embedded tissues. Breast cancer biopsies, organoids, and cell lines were analyzed using the SureQuant method, demonstrating the heterogeneity of kinase protein expression across and within breast cancer clinical subtypes. Kinome quantitation was coupled with nanoscale phosphoproteomics, providing a feasible method for novel clinical diagnosis and understanding of patient kinome responses to treatment.

B-349 Diagnostic Performance of the Atellica IM High-Sensitivity PSA Assay in Men Undergoing Prostate Cancer Screening

Abstract Background This study evaluated the diagnostic performance of the Atellica® IM High-Sensitivity PSA (hsPSA)* assay in men >50 years undergoing prostate cancer (PC) screening in conjunction with digital rectal exam (DRE). Methods Serum samples were collected prospectively from 2671 subjects >50 years referred to a urologist for evaluation of PC from 26 sites across the United States. To establish PC versus benign disease, all subjects underwent a transrectal prostate biopsy ≤60 days after blood draw. At the cutoff of 4.0 ng/mL for the hsPSA assay, the percentage of PCs detected (sensitivity) and corresponding percentage of biopsies avoided in men without PC (specificity) were determined. Results Cancer prevalence (malignant biopsy) was 58.5% (1562/2671) among the diagnostic population. Preliminary results demonstrated that for DRE alone, sensitivity and specificity were 30.9% (482/1562) and 83.0% (920/1109) compared to biopsy. For hsPSA alone at the cutoff of 4.0 ng/mL, sensitivity was 88.7% (1386/1562). The table provides incidence of cancer and positive biopsies by subgroups defined by DRE and hsPSA. hsPSA detected 61.1% (955/1562) of PCs that DRE did not. Of those DRE+, 71.8% (482/671) had positive biopsy. Of those DRE+ and hsPSA ≥4.0 ng/mL, 78.6% (431/548) had positive biopsy, which significantly increased PC detection by 7.0% (95% CI:1.4%-12.5%). Similarly, in the DRE- population, while 54.0% of subjects had positive biopsy, subjects both DRE- and hsPSA <4.0 ng/mL had only 38.5% positive biopsies, a significant difference of 16.5% (95% CI: 6.3%-27.8%). Conclusions Using DRE alone detected only 3 out of 10 patients with PC. It was observed that when used in conjunction with DRE, the hsPSA assay improved both sensitivity and specificity of PC detection over DRE alone. CAUTION: Investigational Device. Not available for sale. Future availability cannot be guaranteed. The results are preliminary and were achieved in unique setting with no expected timeline for completion.

Prognostic and therapeutic implications of tumor-restrictive type III collagen in the breast cancer microenvironment

Collagen plays a critical role in regulating breast cancer progression and therapeutic resistance. An improved understanding of both the features and drivers of tumor-permissive and -restrictive collagen matrices are critical to improve prognostication and develop more effective therapeutic strategies. In this study, using a combination of in vitro, in vivo and bioinformatic experiments, we show that type III collagen (Col3) plays a tumor-restrictive role in human breast cancer. We demonstrate that Col3-deficient, human fibroblasts produce tumor-permissive collagen matrices that drive cell proliferation and suppress apoptosis in non-invasive and invasive breast cancer cell lines. In human triple-negative breast cancer biopsy samples, we demonstrate elevated deposition of Col3 relative to type I collagen (Col1) in non-invasive compared to invasive regions. Similarly, bioinformatics analysis of over 1000 breast cancer patient biopsies from The Cancer Genome Atlas BRCA cohort revealed that patients with higher Col3:Col1 bulk tumor expression had improved overall, disease-free, and progression-free survival relative to those with higher Col1:Col3 expression. Using an established 3D culture model, we show that Col3 increases spheroid formation and induces the formation of lumen-like structures that resemble non-neoplastic mammary acini. Finally, our in vivo study shows co-injection of murine breast cancer cells (4T1) with rhCol3-supplemented hydrogels limits tumor growth and decreases pulmonary metastatic burden compared to controls. Taken together, these data collectively support a tumor-suppressive role for Col3 in human breast cancer and suggest that strategies that increase Col3 may provide a safe and effective therapeutic modality to limit recurrence in breast cancer patients.

Calibrating tumor growth and invasion parameters with spectral spatial analysis of cancer biopsy tissues

The reaction-diffusion equation is widely used in mathematical models of cancer. The calibration of model parameters based on limited clinical data is critical to using reaction-diffusion equation simulations for reliable predictions on a per-patient basis. Here, we focus on cell-level data as routinely available from tissue biopsies used for clinical cancer diagnosis. We analyze the spatial architecture in biopsy tissues stained with multiplex immunofluorescence. We derive a two-point correlation function and the corresponding spatial power spectral distribution. We show that this data-deduced power spectral distribution can fit the power spectrum of the solution of reaction-diffusion equations that can then identify patient-specific tumor growth and invasion rates. This approach allows the measurement of patient-specific critical tumor dynamical properties from routinely available biopsy material at a single snapshot in time.

P3.06D.08 ctDNA-NGS Assay (Liquid Biopsy) for Non-Small Cell Lung Cancer: Utility of Plasma Cell-Free DNA and Tissue NGS in Detecting Genetic Mutations

P3.06D.08 ctDNA-NGS Assay (Liquid Biopsy) for Non-Small Cell Lung Cancer: Utility of Plasma Cell-Free DNA and Tissue NGS in Detecting Genetic Mutations

Clinical utility of upfront liquid biopsy in non-small cell lung cancer in the community setting.

316 Background: Molecular diagnosis of advanced non-small cell lung cancer (NSCLC) is critical to guide therapeutic decisions. Blood next generation sequencing (NGS) allows for non-invasive screening for targetable genetic abnormalities. Many studies have validated using the liquid biopsies to screen for resistant mutations at the emergence of treatment failure. However, the clinical utility of liquid biopsy for newly diagnosed NSCLC, as part of a comprehensive molecular profiling, is an area of active research. Methods: Retrospective analysis of the molecular landscape and clinical outcomes in NSCLC patients who had liquid biopsy done between December of 2017 to February of 2022. Patients had EGFR, ALK, ROS-1, and BRAF tested in the tissue, and underwent liquid biopsy for broad molecular profiling. The plasma genotyping was conducted using a 73-gene panel by Guardant 360 test. Actionable mutations were stratified accordingly to the OncoKB database based on the level of preclinical and clinical evidence of drug targetability. Survival analysis was conducted by August of 2023. Results: We enrolled 122 NSCLC patients who 84% were treatment-naïve and 78% had the liquid biopsy performed at the initial diagnosis. We found that 86 patients had oncogenic mutations and 43 (35%) had actionable mutations, with 37 (29%) falling under level 1 of evidence mutations. EGFR and KRAS G12C mutations were the two most common level 1 genetic abnormalities (23% and 11% of all actionable mutations, respectively). We identified two germline BRCA carriers who were referred for genetic counselling. 25 patients (20%) received treatment based on the liquid biopsy results, with 15 (12%) achieving partial response. Six patients had liquid biopsy done at progression of EGFR or MET therapies, which identified a resistance mechanism in three of them. Conclusions: Upfront liquid biopsy identified a significant proportion of patients with targetable mutations. Here, we reported actionable mutations in 35% of our patients who 84% had no prior systemic treatment. Our results complement prior literature and shows that blood next generation sequencing can be a useful tool to guide upfront therapeutical options at the community healthcare setting.

Liquid Biopsy in Lung Cancer: Nano–Flow Cytometry Detection of Non–Small Cell Lung Cancer in Blood

Non–small cell lung cancer (NSCLC) remains a leading cause of global mortality, with current screening and diagnostic methods often lacking in sensitivity and specificity. In our endeavor to develop precise, objective, and easily accessible diagnostic biomarkers for NSCLC, this study aimed to leverage rapidly evolving liquid biopsy techniques in the field of pathology to differentiate NSCLC patients from healthy controls by isolating peripheral blood samples and enriching extracellular vesicles (EVs) containing lung-derived proteins (thyroid transcription factor-1 [TTF-1] and surfactant protein B [SFTPB]), along with the cancer-associated protein CD151+ EVs. Additionally, for practical applications, we established a nano–flow cytometry assay to detect plasma EVs readily. NSCLC patients demonstrated significantly reduced counts of TTF-1+ EVs and CD151+ EVs in plasma compared with healthy controls (P < .0001), whereas SFTPB+ EVs showed no significant difference (P > .05). Integrated analysis of TTF-1+, CD151+, and SFTPB+ EVs yielded an area under the curve values of 0.913 and 0.854 in the discovery and validation cohorts, respectively. Thus, although further validation is essential, the newly developed technologies are of great significance for the robust detection of NSCLC biomarkers.

The role of Cabazitaxel in patients with castration-resistant and osseous metastases prostate cancer. A Hellenic Cooperative Oncology Group Phase II Study.: Cabazitaxel in mCRPC patients with osseous metastases

BackgroundCabazitaxel is an effective treatment in metastatic castration-resistant prostate cancer (mCRPC) patients previously exposed to docetaxel and novel hormonal treatments. Understanding the molecular biology of mCRPC disease and taking into account the several approved treatment options, biomarkers are needed to guide decision making including cabazitaxel treatment. MethodsCababone was a phase II translational study that attempted to identify predictors of cabazitaxel efficacy. mCRPC with documented bone metastases were enrolled prospectively and treated with cabazitaxel 25mg/m2 every three weeks. Prostate cancer biopsies, bone marrow aspirates and blood samples were collected for translational research. ResultsSixty patients were enrolled and 59 received treatment according to protocol. Six-month progression free survival (PFS) rate was 47% (95% CI: 33% - 59%) and 12-month Overall Survival (OS) rate was 70% (95% CI: 56% - 80%). Patients with reactive hematopoiesis had improved PFS and OS with cabazitaxel treatment. Mutations in HRR genes were detected in 7 patients. ConclusionsNo differences in cabazitaxel efficacy were noted according to mutational status of HRR genes analyzed. No new safety issues were detected. In conclusion, CabaBone confirmed efficacy of cabazitaxel in mCRPC patients including the subgroup of patients with HRR mutations. Reactive hematopoiesis in bone marrow biopsies was related to improved survival warranting further investigation of bone biomarkers as predictors of cabazitaxel efficacy. Micro-AbstactCabaBone is a phase II translational study that evaluated the role of bone microenvironment and HRR genes mutations in the efficacy of cabazitaxel in mCRPC patients with bone-only disease. Study confirmed efficacy of cabazitaxel in patients independent of the presence of HRR gene mutations. Reactive hematopoiesis in bone marrow was recognized as a possible predictive and prognostic biomarker of cabazitaxel efficacy.

Estrogen receptor beta (ERβ) in esophageal cancer - a systematic review and meta-analysis.

Esophageal cancer is the eighth most common cause of cancer-related deaths worldwide. There are two main histological subtypes of esophageal cancer: adenocarcinoma and squamous cell carcinoma. Among the factors associated with the development of esophageal cancer, estrogen receptor beta (ERβ) has been found to have a clinical significance. To investigate the relationship between ERβ expression and esophageal cancer. English Medical literature searches were conducted for ERβ expression in patients with esophageal cancer versus healthy controls. Searches were performed up to August 31, 2023, using MEDLINE, PubMed, Embase and Google Scholar. Meta-analysis was performed by using Comprehensive meta-analysis software (Version 4, Biostat Inc., Englewood, NJ, USA). Pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated. Heterogeneity was evaluated using Cochrane Q-test, and it was considered present if the Q-test P value was less than 0.10. I2 statistic was used to measure the proportion of inconsistency in individual studies, with I2 > 50% representing heterogeneity. We also calculated a potential publication bias. Ten studies representing 11 substudies were selected according to the inclusion criteria. The odds ratio of ERβ expression in fixed effect analysis was 0.448, 95% CI: 0.237 to 0.846, 55.2% lower in esophageal cancer than in normal mucosa. Heterogeneity and inconsistency were low, and no publication bias was demonstrated. This meta-analysis showed that ERβ expression is lower in esophageal cancer biopsy specimens than in healthy controls, this finding may have a significant effect on survival and can lead to new therapeutic avenues.

Liquid and Tissue Biopsies for Lung Cancer: Algorithms and Perspectives.

The targeted therapies and immunotherapies in thoracic oncology, particularly for NS-NSCLC, are associated with an increase in the number of predictive biomarkers to be assessed in routine clinical practice. These treatments are administered thanks to marketing authorization for use in daily practice or are evaluated during clinical trials. Since the molecular targets to be identified are more and more complex and numerous, it is now mandatory to use NGS. NGS can be developed from both tissue and fluid (mainly blood). The blood tests in oncology, so-called "liquid biopsies" (LB), are performed with plasmatic circulating free DNA (cf-DNA) and are complementary to the molecular testing performed with a TB. LB use in lung cancer is associated with international guidelines, but additional algorithms could be set up. However, even if useful for better care of patients, notably with advanced and metastatic NS-NSCLC, until now LB are not often integrated into daily practice, at least in Europe and notably in France. The purpose of this review is to describe the different opportunities and algorithms leading to the identification of the molecular signature of NS-NSCLC, using both tissue and liquid biopsies, and to introduce the principle limitations but also some perspectives in this field.

Systematic Modeling of Risk-Associated Copy Number Alterations in Cancer.

The determination of the cancer prognosis is paramount for patients and medical personnel so that they can devise treatment strategies. Transcriptional-based signatures and subtypes derived from cancer biopsy material have been used in clinical practice for several cancer types to aid in setting the patient prognosis and forming treatment strategies. Other genomic features in cancer biopsies, such as copy number alterations (CNAs), have been underused in clinical practice, and yet they represent a complementary source of molecular information that can add detail to the prognosis, which is supported by recent work in breast, ovarian, and lung cancers. Here, through a systematic strategy, we explored the prognostic power of CNAs in 37 cancer types. In this analysis, we defined two modes of informative features, deep and soft, depending on the number of alleles gained or lost. These informative modes were grouped by amplifications or deletions to form four single-data prognostic models. Finally, the single-data models were summed or combined to generate four additional multidata prognostic models. First, we show that the modes of features are cancer-type dependent, where deep alterations generate better models. Nevertheless, some cancers require soft alterations to generate a feasible model due to the lack of significant deep alterations. Then, we show that the models generated by summing coefficients from amplifications and deletions appear to be more practical for many but not all cancer types. We show that the CNA-derived risk group is independent of other clinical factors. Furthermore, overall, we show that CNA-derived models can define clinically relevant risk groups in 33 of the 37 (90%) cancer types analyzed. Our study highlights the use of CNAs as biomarkers that are potentially clinically relevant to survival in cancer patients.

Length-scale study in deep learning prediction for non-small cell lung cancer brain metastasis

Deep learning-assisted digital pathology has demonstrated the potential to profoundly impact clinical practice, even surpassing human pathologists in performance. However, as deep neural network (DNN) architectures grow in size and complexity, their explainability decreases, posing challenges in interpreting pathology features for broader clinical insights into physiological diseases. To better assess the interpretability of digital microscopic images and guide future microscopic system design, we developed a novel method to study the predictive feature length-scale that underpins a DNN’s predictive power. We applied this method to analyze a DNN’s capability in predicting brain metastasis from early-stage non-small-cell lung cancer biopsy slides. This study quantifies DNN’s attention for brain metastasis prediction, targeting features at both the cellular scale and tissue scale in H&E-stained histological whole slide images. At the cellular scale, the predictive power of DNNs progressively increases with higher resolution and significantly decreases when the resolvable feature length exceeds 5 microns. Additionally, DNN uses more macro-scale features associated with tissue architecture and is optimized when assessing visual fields greater than 41 microns. Our study computes the length-scale requirements for optimal DNN learning on digital whole-slide microscopic images, holding the promise to guide future optical microscope designs in pathology applications and facilitating downstream deep learning analysis.

Prediction of High Nodal Burden in Patients With Sentinel Node–Positive Luminal ERBB2-Negative Breast Cancer

In patients with clinically node-negative (cN0) breast cancer and 1 or 2 sentinel lymph node (SLN) macrometastases, omitting completion axillary lymph node dissection (CALND) is standard. High nodal burden (≥4 axillary nodal metastases) is an indication for intensified treatment in luminal breast cancer; hence, abstaining from CALND may result in undertreatment. To develop a prediction model for high nodal burden in luminal ERBB2-negative breast cancer (all histologic types and lobular breast cancer separately) without CALND. The prospective Sentinel Node Biopsy in Breast Cancer: Omission of Axillary Clearance After Macrometastases (SENOMAC) trial randomized patients 1:1 to CALND or its omission from January 2015 to December 2021 among adult patients with cN0 T1-T3 breast cancer and 1 or 2 SLN macrometastases across 5 European countries. The cohort was randomly split into training (80%) and test (20%) sets, with equal proportions of high nodal burden. Prediction models were developed by multivariable logistic regression in the complete luminal ERBB2-negative cohort and a lobular breast cancer subgroup. Nomograms were constructed. The present diagnostic/prognostic study presents the results of a prespecified secondary analysis of the SENOMAC trial. Herein, only patients with luminal ERBB2-negative tumors assigned to CALND were selected. Data analysis for this article took place from June 2023 to April 2024. Predictors of high nodal burden. High nodal burden was defined as ≥4 axillary nodal metastases. The luminal prediction model was evaluated regarding discrimination and calibration. Of 1010 patients (median [range] age, 61 [34-90] years; 1006 [99.6%] female and 4 [0.4%] male), 138 (13.7%) had a high nodal burden and 212 (21.0%) had lobular breast cancer. The model in the training set (n = 804) included number of SLN macrometastases, presence of SLN micrometastases, SLN ratio, presence of SLN extracapsular extension, and tumor size (not included in lobular subgroup). Upon validation in the test set (n = 201), the area under the receiver operating characteristic curve (AUC) was 0.74 (95% CI, 0.62-0.85) and the calibration was satisfactory. At a sensitivity threshold of ≥80%, all but 5 low-risk patients were correctly classified corresponding to a negative predictive value of 94%. The prediction model for the lobular subgroup reached an AUC of 0.74 (95% CI, 0.66-0.83). The predictive models and nomograms may facilitate systemic treatment decisions without exposing patients to the risk of arm morbidity due to CALND. External validation is needed. ClinicalTrials.gov Identifier: NCT02240472.

Nanoscale Extracellular Vesicle-Enabled Liquid Biopsy: Advances and Challenges for Lung Cancer Detection.

Lung cancer is responsible for the death of over a million people worldwide every year. With its high mortality rate and exponentially growing number of new cases, lung cancer is a major threat to public health. The high mortality and poor survival rates of lung cancer patients can be attributed to its stealth progression and late diagnosis. For a long time, intrusive tissue biopsy has been considered the gold standard for lung cancer diagnosis and subtyping; however, the intrinsic limitations of tissue biopsy cannot be overlooked. In addition to being invasive and costly, it also suffers from limitations in sensitivity and specificity, is not suitable for repeated sampling, provides restricted information about the tumor and its molecular landscape, and is inaccessible in several cases. To cope with this, advancements in diagnostic technologies, such as liquid biopsy, have shown great prospects. Liquid biopsy is an innovative non-invasive approach in which cancer-related components called biomarkers are detected in body fluids, such as blood, urine, saliva and others. It offers a less invasive alternative with the potential for applications such as routine screening, predicting treatment outcomes, evaluating treatment effectiveness, detecting residual disease, or disease recurrence. A large number of research articles have indicated extracellular vesicles (EVs) as ideal biomarkers for liquid biopsy. EVs are a heterogeneous collection of membranous nanoparticles with diverse sizes, contents, and surface markers. EVs play a critical role in pathophysiological states and have gained prominence as diagnostic and prognostic biomarkers for multiple diseases, including lung cancer. In this review, we provide a detailed overview of the potential of EV-based liquid biopsy for lung cancer. Moreover, it highlights the strengths and weaknesses of various contemporary techniques for EV isolation and analysis in addition to the challenges that need to be addressed to ensure the widespread clinical application of EV-based liquid biopsies for lung cancer. In summary, EV-based liquid biopsies present interesting opportunities for the development of novel diagnostic and prognostic platforms for lung cancer, one of the most abundant cancers responsible for millions of cancer-related deaths worldwide.

Semen sEV tRF-Based Models Increase Non-Invasive Prediction Accuracy of Clinically Significant Prostate Cancer among Patients with Moderately Altered PSA Levels.

PSA screening has led to an over-diagnosis of prostate cancer (PCa) and unnecessary biopsies of benign conditions due to its low cancer specificity. Consequently, more accurate, preferentially non-invasive, tests are needed. We aim to evaluate the potential of semen sEV (small extracellular vesicles) tsRNAs (tRNA-derived small RNAs) as PCa indicators. Initially, following a literature review in the OncotRF database and high-throughput small RNA-sequencing studies in PCa tissue together with the sncRNA profile in semen sEVs, we selected four candidate 5'tRF tsRNAs for validation as PCa biomarkers. RT-qPCR analysis in semen sEVs from men with moderately elevated serum PSA levels successfully shows that the differential expression of the four tRFs between PCa and healthy control groups can be detected in a non-invasive manner. The combined model incorporating PSA and specific tRFs (5'-tRNA-Glu-TTC-9-1_L30 and 5'-tRNA-Val-CAC-3-1_L30) achieved high predictive accuracy in identifying samples with a Gleason score ≥ 7 and staging disease beyond IIA, supporting that the 5'tRF fingerprint in semen sEV can improve the PSA predictive value to discriminate between malignant and indolent prostate conditions. The in silico study allowed us to map target genes for the four 5'tRFs possibly involved in PCa. Our findings highlight the synergistic use of multiple biomarkers as an efficient approach to improve PCa screening and prognosis.