N-staging is a determining factor for prognostic assessment and decision-making for stage-based cancer therapeutic strategies. Visual inspection of whole-slides of intact lymph nodes is currently the ...main method used by pathologists to calculate the number of metastatic lymph nodes (MLNs). Moreover, even at the same N stage, the outcome of patients varies dramatically. Here, we propose a deep-learning framework for analyzing lymph node whole-slide images (WSIs) to identify lymph nodes and tumor regions, and then to uncover tumor-area-to-MLN-area ratio (T/MLN). After training, our model's tumor detection performance was comparable to that of experienced pathologists and achieved similar performance on two independent gastric cancer validation cohorts. Further, we demonstrate that T/MLN is an interpretable independent prognostic factor. These findings indicate that deep-learning models could assist not only pathologists in detecting lymph nodes with metastases but also oncologists in exploring new prognostic factors, especially those that are difficult to calculate manually.
•We revealed the practicability of NIC and λHU from spectral CT of LM in lung cancer.•The NIC and λHU of patients with LM was significantly lower than that of non-LM patients.•NIC and λHU in the ...arterial phase identified lymphatic metastasis better than short-axis diameter.
This study evaluated the use of quantitative spectral computed tomography (CT) parameters to identify lymph node metastasis (LM) in lung cancer.
Literature about LM in lung cancer diagnosed using spectral CT up to September 2022 was retrieved from the PubMed, EMBASE, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure, and Wanfang databases. The literature was strictly screened according to the inclusion and exclusion criteria. Data were extracted, quality assessment was performed, and heterogeneity was evaluated. The pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (+LR), -LR, and diagnostic odds ratio (DOR) for normalized iodine concentration (NIC) and spectral attenuation curve (λHU) were calculated. The subject receiver operating characteristic (SROC) curves were used, and the area under the curve (AUC) was calculated.
Eleven studies, including 1,290 cases, without obvious publication bias were enrolled. In eight articles, the pooled AUC of NIC in the arterial phase (AP) was 0.84 (SEN = 0.85, SPE = 0.74, +LR = 3.3, −LR = 0.20, DOR = 16) while that of NIC in the venous phase (VP) was 0.82 (SEN = 0.78, SPE = 0.72). Additionally, the pooled AUC for λHU (AP) was 0.87 (SEN = 0.74, SPE = 0.84, +LR = 4.5, −LR = 0.31, DOR = 15) and that for λHU (VP) was 0.81 (SEN = 0.62, SPE = 0.81). Lymph node (LN) short-axis diameter was ranked last, with a pooled AUC of 0.81 (SEN = 0.69, SPE = 0.79).
Spectral CT is a suitable noninvasive and cost-effective method for determining LM in lung cancer. Additionally, NIC and λHU in the AP have good discrimination ability than short-axis diameter, providing a valuable basis and reference for preoperative evaluation.
As one effective treatment for lateral pelvic lymph node (LPLN) metastasis (LPNM), laparoscopic LPLN dissection (LPND) is limited due to the complicated anatomy of the pelvic sidewall and various ...complications after surgery. With regard to improving the accuracy and completeness of LPND as well as safety, we tried an innovative method using indocyanine green (ICG) visualized with a near-infrared (NIR) camera system to guide the detection of LPLNs in patients with middle-low rectal cancer.
To investigate whether ICG-enhanced NIR fluorescence-guided imaging is a better technique for LPND in patients with rectal cancer.
A total of 42 middle-low rectal cancer patients with clinical LPNM who underwent total mesorectal excision (TME) and LPND between October 2017 and March 2019 at our institution were assessed and divided into an ICG group and a non-ICG group. Clinical characteristics, operative outcomes, pathological outcomes, and postoperative complication information were compared and analysed between the two groups.
Compared to the non-ICG group, the ICG group had significantly lower intraoperative blood loss (55.8 ± 37.5 mL
108.0 ± 52.7 mL,
= 0.003) and a significantly larger number of LPLNs harvested (11.5 ± 5.9
7.1 ± 4.8,
= 0.017). The LPLNs of two patients in the non-IVG group were residual during LPND. In addition, no significant difference was found in terms of LPND, LPNM, operative time, conversion to laparotomy, preoperative complication, or hospital stay (
> 0.05).
ICG-enhanced NIR fluorescence-guided imaging could be a feasible and convenient technique to guide LPND because it could bring specific advantages regarding the accuracy and completeness of surgery as well as safety.
Sentinel lymph node (SLN) excision is included in various cancer guidelines to identify microscopic metastatic disease. Although effective, SLN excision is an invasive procedure requiring radioactive ...tracing. Novel imaging approaches assessing SLN metastatic status could improve or replace conventional lymph node excision protocols. In our first-in-human study, we used noninvasive multispectral optoacoustic tomography (MSOT) to image SLNs ex vivo and in vivo in patients with melanoma, to determine metastatic status. MSOT significantly improved the tumor metastasis detection rate in excised SLN (506 SLNs from 214 melanoma patients) compared with the conventional EORTC (European Organisation for Research and Treatment of Cancer) Melanoma Group protocol (22.9% versus 14.2%). MSOT combined with the near-infrared fluorophore indocyanine green reliably visualized SLNs in vivo in 20 patients, up to 5-cm penetration and with 100% concordance with (99m)Tc-marked SLN lymphoscintigraphy. MSOT identified cancer-free SLNs in vivo and ex vivo without a single false negative (189 total lymph nodes), with 100% sensitivity and 48 to 62% specificity. Our findings indicate that a noninvasive, nonradioactive MSOT-based approach can identify and determine SLN status and confidently rule out the presence of metastasis. The study further demonstrates that optoacoustic imaging strategies can improve the identification of SLN metastasis as an alternative to current invasive SLN excision protocols.
Mechanisms underlying global changes in gene expression during tumour progression are poorly understood. SATB1 is a genome organizer that tethers multiple genomic loci and recruits ...chromatin-remodelling enzymes to regulate chromatin structure and gene expression. Here we show that SATB1 is expressed by aggressive breast cancer cells and its expression level has high prognostic significance (P < 0.0001), independent of lymph-node status. RNA-interference-mediated knockdown of SATB1 in highly aggressive (MDA-MB-231) cancer cells altered the expression of >1,000 genes, reversing tumorigenesis by restoring breast-like acinar polarity and inhibiting tumour growth and metastasis in vivo. Conversely, ectopic SATB1 expression in non-aggressive (SKBR3) cells led to gene expression patterns consistent with aggressive-tumour phenotypes, acquiring metastatic activity in vivo. SATB1 delineates specific epigenetic modifications at target gene loci, directly upregulating metastasis-associated genes while downregulating tumour-suppressor genes. SATB1 reprogrammes chromatin organization and the transcription profiles of breast tumours to promote growth and metastasis; this is a new mechanism of tumour progression.
Germ cell tumours predominantly of the testis ((T)GCTs) are remarkably chemotherapy sensitive. However, a small proportion of patients fail to be cured with cisplatin‐based combination chemotherapy. ...miR‐371a‐3p is a new liquid biopsy biomarker for (T)GCTs. The aim of this study was to evaluate clinical utility of plasma miR‐371a‐3p level in patients starting systemic chemotherapy. Patients were included before the first cycle (N = 180) and second cycle (N = 101) of systemic first line chemotherapy, treated between July 2010 and May 2017. Plasma miR‐371a‐3p levels were measured with the ampTSmiR test and compared to disease characteristics and outcome. Pretreatment plasma miR‐371a‐3p levels were increased in 51.7% of cases and associated with number of metastatic sites, presence of lung, retroperitoneal, and mediastinal lymph node metastases, S – stage, IGCCCG risk group, and response to therapy. Patients with a negative pretreatment plasma level had better progression‐free survival (PFS) and overall survival (OS) compared to patients being positive for miR‐371a‐3p (hazard ratio HR = 0.26, 95% confidence interval CI 0.09‐0.71, P = 0.02 for PFS and HR = 0.21, 95% CI 0.07‐0.67, P = 0.03 for OS, respectively). Patients negative for miR‐371a‐3p in both samples had a superior PFS (HR = 0.10, 95% CI 0.01‐21.49, P = 0.02) and OS (HR = 0.08, 95% CI 0.01‐27.81, P = 0.008) compared to patients with miR‐371a‐3p positive in both samples (multivariate analyses were non‐significant). In total 68% of the patients were S0. This study demonstrates clinical value of plasma miR‐371a‐3p level in chemotherapy naïve (T)GCT patients starting first line of chemotherapy to predict prognosis.
Tumor-draining lymph node (TDLN) invasion by metastatic cells in breast cancer correlates with poor prognosis and is associated with local immunosuppression, which can be partly mediated by ...regulatory T cells (Tregs). Here, we study Tregs from matched tumor-invaded and non-invaded TDLNs, and breast tumors. We observe that Treg frequencies increase with nodal invasion, and that Tregs express higher levels of co-inhibitory/stimulatory receptors than effector cells. Also, while Tregs show conserved suppressive function in TDLN and tumor, conventional T cells (Tconvs) in TDLNs proliferate and produce Th1-inflammatory cytokines, but are dysfunctional in the tumor. We describe a common transcriptomic signature shared by Tregs from tumors and nodes, including CD80, which is significantly associated with poor patient survival. TCR RNA-sequencing analysis indicates trafficking between TDLNs and tumors and ongoing Tconv/Treg conversion. Overall, TDLN Tregs are functional and express a distinct pattern of druggable co-receptors, highlighting their potential as targets for cancer immunotherapy.
Background
Breast cancer (BC) is among the most common cancers worldwide. Machine learning–based radiomics model could predict axillary lymph node metastasis (ALNM) of BC accurately.
Purpose
The ...purpose is to develop a machine learning model to predict ALNM of BC by focusing on the radiomics features of axillary lymphatic node (ALN).
Methods
A group of 398 BC patients with 800 ALNs were retrospectively collected. A set of patient characteristics were obtained to form clinical factors. Three hundred and twenty‐six radiomics features were extracted from each region of interest for ALN in contrast‐enhanced computed tomography (CECT) image. A framework composed of four feature selection methods and 14 machine learning classification algorithms was systematically applied. A clinical model, a radiomics model, and a combined model were developed using a cross‐validation approach and compared. Metrics of the area under the curve (AUC), accuracy, sensitivity, and specificity were calculated to evaluate the performance of these models in the prediction of ALNM in BC.
Results
Among the 800 cases of ALNs, there were 388 cases of positive metastasis (48.50%) and 412 cases of negative metastasis (51.50%). The baseline clinical model achieved the performance with an AUC = 0.8998 (95% CI 0.8540, 0.9457). The radiomics model achieved an AUC = 0.9081 (95% CI 0.8640, 0.9523). The combined model using the clinical factors and radiomics features achieved the best results with an AUC = 0.9305 (95% CI 0.8928, 0.9682).
Conclusions
Combinations of feature selection methods and machine learning‐based classification algorithms can develop promising predictive models to predict ALNM in BC using CECT features. The combined model of clinical factors and radiomics features outperforms both the clinical model and the radiomic model.
Objectives
To evaluate quantification of iodine uptake in metastatic and non-metastatic lymph nodes (LNs) by dual-energy CT (DECT) and to assess if the distribution of iodine within LNs at DECT ...correlates with the pathological structure.
Methods
Ninety LNs from 37 patients (23 with lung and 14 with gynaecological malignancies) were retrospectively selected. Information of LNs sent for statistical analysis included Hounsfield units (HU) at different energy levels; decomposition material densities fat–iodine, iodine–fat, iodine–water, water–iodine. Statistical analysis included evaluation of interobserver variability, material decomposition densities and spatial HU distribution within LNs.
Results
Interobserver agreement was excellent. There was a significant difference in iodine–fat and iodine–water decompositions comparing metastatic and non-metastatic LNs (
p
< 0.001); fat–iodine and water–iodine did not show significant differences. HU distribution showed a significant gradient from centre to periphery within non-metastatic LNs that was significant up to 20–30% from the centre, whereas metastatic LNs showed a more homogeneous distribution of HU, with no significant gradient.
Conclusions
DECT demonstrated a lower iodine uptake in metastatic compared to non-metastatic LNs. Moreover, the internal iodine distribution showed an evident gradient of iodine distribution from centre to periphery in non-metastatic LNs, and a more homogeneous distribution within metastatic LNs, which corresponded to the pathological structure.
Key points
• This study demonstrated a lower iodine uptake in metastatic than non-metastatic LNs.
• Internal distribution of HU was different between metastatic and non-metastatic lymph nodes.
• The intranodal iodine distribution disclosed a remarkable correlation with the histological LN structure.
Tumor-associated macrophages (TAMs) are major innate immune cells that constitute up to 50% of the cell mass of human tumors. TAMs are highly heterogeneous cells that originate from resident ...tissue-specific macrophages and from newly recruited monocytes. TAMs' variability strongly depends on cancer type, stage, and intratumor heterogeneity. Majority of TAMs are programmed by tumor microenvironment to support primary tumor growth and metastatic spread. However, TAMs can also restrict tumor growth and metastasis. In this review, we summarized the knowledge about the role of TAMs in tumor growth, metastasis and in the response to cancer therapy in patients with five aggressive types of cancer: breast, colorectal, lung, ovarian, and prostate cancers that are frequently metastasize into distant organs resulting in high mortality of the patients. Two major TAM parameters are applied for the evaluation of TAM correlation with the cancer progression: total amount of TAMs and specific phenotype of TAMs identified by functional biomarkers. We summarized the data generated in the wide range of international patient cohorts on the correlation of TAMs with clinical and pathological parameters of tumor progression including lymphatic and hematogenous metastasis, recurrence, survival, therapy efficiency. We described currently available biomarkers for TAMs that can be measured in patients' samples (tumor tissue and blood). CD68 is the major biomarker for the quantification of total TAM amounts, while transmembrane receptors (stabilin-1, CD163, CD206, CD204, MARCO) and secreted chitinase-like proteins (YKL-39, YKL-40) are used as biomarkers for the functional TAM polarization. We also considered that specific role of TAMs in tumor progression can depend on the localization in the intratumoral compartments. We have made the conclusion for the role of TAMs in primary tumor growth, metastasis, and therapy sensitivity for breast, colorectal, lung, ovarian, and prostate cancers. In contrast to other cancer types, majority of clinical studies indicate that TAMs in colorectal cancer have protective role for the patient and interfere with primary tumor growth and metastasis. The accumulated data are essential for using TAMs as biomarkers and therapeutic targets to develop cancer-specific immunotherapy and to design efficient combinations of traditional therapy and new immunomodulatory approaches.Tumor-associated macrophages (TAMs) are major innate immune cells that constitute up to 50% of the cell mass of human tumors. TAMs are highly heterogeneous cells that originate from resident tissue-specific macrophages and from newly recruited monocytes. TAMs' variability strongly depends on cancer type, stage, and intratumor heterogeneity. Majority of TAMs are programmed by tumor microenvironment to support primary tumor growth and metastatic spread. However, TAMs can also restrict tumor growth and metastasis. In this review, we summarized the knowledge about the role of TAMs in tumor growth, metastasis and in the response to cancer therapy in patients with five aggressive types of cancer: breast, colorectal, lung, ovarian, and prostate cancers that are frequently metastasize into distant organs resulting in high mortality of the patients. Two major TAM parameters are applied for the evaluation of TAM correlation with the cancer progression: total amount of TAMs and specific phenotype of TAMs identified by functional biomarkers. We summarized the data generated in the wide range of international patient cohorts on the correlation of TAMs with clinical and pathological parameters of tumor progression including lymphatic and hematogenous metastasis, recurrence, survival, therapy efficiency. We described currently available biomarkers for TAMs that can be measured in patients' samples (tumor tissue and blood). CD68 is the major biomarker for the quantification of total TAM amounts, while transmembrane receptors (stabilin-1, CD163, CD206, CD204, MARCO) and secreted chitinase-like proteins (YKL-39, YKL-40) are used as biomarkers for the functional TAM polarization. We also considered that specific role of TAMs in tumor progression can depend on the localization in the intratumoral compartments. We have made the conclusion for the role of TAMs in primary tumor growth, metastasis, and therapy sensitivity for breast, colorectal, lung, ovarian, and prostate cancers. In contrast to other cancer types, majority of clinical studies indicate that TAMs in colorectal cancer have protective role for the patient and interfere with primary tumor growth and metastasis. The accumulated data are essential for using TAMs as biomarkers and therapeutic targets to develop cancer-specific immunotherapy and to design efficient combinations of traditional therapy and new immunomodulatory approaches.
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