Abstract A large variety of cancers are associated with a high incidence of lymph node metastasis, which leads to a high risk of cancer death. Herein, we demonstrate that multimodal imaging guided ...photothermal therapy can inhibit tumor metastasis after surgery by burning the sentinel lymph nodes (SLNs) with metastatic tumor cells. A near-infrared dye, IR825, is absorbed onto human serum albumin (HSA), which is covalently linked with diethylenetriamine pentaacetic acid (DTPA) molecules to chelate gadolinium. The formed HSA-Gd-IR825 nanocomplex exhibits strong fluorescence together with high near-infrared (NIR) absorbance, and in the mean time could serve as a T1 contrast agent in magnetic resonance (MR) imaging. In vivo bi-modal fluorescence and MR imaging uncovers that HSA-Gd-IR825 after being injected into the primary tumor would quickly migrate into tumor-associated SLNs through lymphatic circulation. Utilizing the strong NIR absorbance of HSA-Gd-IR825, SLNs with metastatic cancer cells can be effectively ablated under exposure to a NIR laser. Such treatment when combined with surgery to remove the primary tumor offers remarkable therapeutic outcomes in greatly inhibiting further metastatic spread of cancer cells and prolonging animal survival. Our work presents an albumin-based theranostic nano-probe with functions of multimodal imaging and photothermal therapy, together with a ‘photothermal ablation assisted surgery’ strategy, promising for future clinical cancer treatment.
To explore an MRI-based radiomics nomogram for preoperatively predicting of pelvic lymph node (PLN) metastasis in patients with early-stage cervical cancer (ECC).
Ninety-six patients with ECC were ...enrolled in this study. All patients underwent T2WI and DWI scans before radical hysterectomy with PLN dissection surgery. Radiomics features extracted from T2WI and DWI were selected by least absolute shrinkage and selection operation regression for further radimoics signature calculation. The discrimination of this radiomics signature for PLN metastasis was then assessed using a support vector machine (SVM) model. Subsequently, a radiomics nomogram was constructed based on the radiomics signature and clinicopathologic risk factors using a multivariable logistic regression method. The performance of the radiomics nomogram for the preoperative prediction of PLN metastasis was evaluated for discrimination and calibration.
The radiomics signatures demonstrated a good discrimination for PLN metastasis. A radiomics signature derived from joint T2WI and DWI yielded higher AUC than the signatures derived from T2WI or DWI alone. The radiomics nomogram integrating the radiomics signature with clinicopathologic risk factors showed a significant improvement over the nomogram based only on clinicopathologic risk factors in the primary cohort(C-index, 0.893 vs. 0.616; P = 4.311×10-5) and validation cohort(C-index, 0.922 vs. 0.799; P = 3.412 ×10-2).The calibration curves also showed good agreement.
The radiomics nomogram based on joint T2WI and DWI demonstrated an improved prediction ability for PLN metastasis in ECC. This noninvasive and convenient tool may be used to facilitate preoperative identification of PLN metastasis in patients with ECC.
To determine whether the tumor immune infiltrate, as recently evaluated with the Immunoscore methodology, could be a useful prognostic marker in patients with rectal cancers.
The influence of the ...immune infiltrate on patient's outcome was investigated in patients with or without preoperative chemoradiation therapy (pCRT). The density of total (CD3(+)) and cytotoxic (CD8(+)) T lymphocytes was evaluated by immunohistochemistry and quantified by a dedicated image analysis software in surgical specimens of patients with rectal cancer (n = 111) who did not receive pCRT and in tumor biopsies performed before pCRT from additional 55 patients. The results were correlated with tumor recurrence, patient's survival, and response to pCRT.
The densities of CD3(+) and CD8(+) lymphocytes and the associated Immunoscore (from I0 to I4) were significantly correlated with differences in disease-free and overall survival (HR, 1.81 and 1.72, respectively; all P < 0.005). Cox multivariate analysis supports the advantage of the Immunoscore compared with the tumor-node-metastasis (TNM) staging in predicting recurrence and survival (all P < 0.001). Lymph node ratio added information in a prognostic model (all P < 0.05). In addition, high infiltration of CD3(+) and CD8(+) lymphocytes in tumor biopsies was associated with downstaging of the tumor after pCRT (CD3(+) cells; Fisher exact test P = 0.01).
The Immunoscore could be a useful prognostic marker in patients with rectal cancer treated by primary surgery. The determination of the immune infiltrate in biopsies before treatment could be a valuable information for the prediction of response to pCRT.
Exosomes have been demonstrated as an important factor to influence cancer invasion and metastasis. Previous studies have shown that CXC chemokine recepter-4 (CXCR4) and stromal cell-derived ...factor-1α (SDF-1α) mediates matrix metalloproteinases (MMPs) secretions to facilitate lymph node metastasis of hepatocarcinoma cells. In this study, we demonstrated that exosomes containing elevated CXCR4 from high lymph node metastatic mouse hepatocarcinoma Hca-F cells were able to promote the migration and invasion of a paired syngeneic Hca-P cells that have low metastatic potential. Such impact on enhanced migratory and invasive capacities of Hca-P cells was triggered by the internalization of exosomes isolated from Hca-F cells. This was possibly due to the horizontal transferring of CXCR4 via exosomes. The lymphatic endothelial cells (LECs) increased the migration and invasion of Hca-F cells probably by expressing SDF-1α which bound with CXCR4 in the Hca-F cells and subsequently enhanced the secretions of MMP-9, MMP-2 and vascular endothelial growth factor C (VEGF-C). Exosomal CXCR4 from Hca-F cells promoted LECs proliferative rate and lymphatic tube formation ability. Our findings suggest that horizontal transfer of exosomal CXCR4 can promote murine hepatocarcinoma cell migration, invasion and lymphangiogenesis, and exosomal CXCR4 might be a novel therapeutic target against tumor lymphatic metastasis.
•Horizontal transfer of exosomal CXCR4 promotes Hca-P cell migration and invasion.•SDF-1α/CXCR4 axis mediated MMP-9, MMP-2 and VEGF-C attracts Hca-F cells to LECs.•Exosomal CXCR4 from Hca-F cells enhances LECs proliferation and lymphangiogenesis.•Exosomal CXCR4 maybe a novel therapeutic target of tumor lymphatic metastasis.
Background
The SUCCOR cohort was developed to analyse the overall and disease-free survival at 5 years in women with FIGO 2009 stage IB1 cervical cancer. The aim of this study was to compare the use ...of adjuvant therapy in these women, depending on the method used to diagnose lymphatic node metastasis.
Patients and Methods
We used data from the SUCCOR cohort, which collected information from 1049 women with FIGO 2009 stage IB1 cervical cancer who were operated on between January 2013 and December 2014 in Europe. We calculated the adjusted proportion of women who received adjuvant therapy depending on the lymph node diagnosis method and compared disease free and overall survival using Cox proportional-hazards regression models. Inverse probability weighting was used to adjust for baseline potential confounders.
Results
The adjusted proportion of women who received adjuvant therapy was 33.8% in the sentinel node biopsy + lymphadenectomy (SNB+LA) group and 44.7% in the LA group (
p
= 0.02), although the proportion of positive nodal status was similar (
p
= 0.30). That difference was greater in women with negative nodal status and positive Sedlis criteria (difference 31.2%,
p
= 0.01). Here, those who underwent a SNB+LA had an increased risk of relapse hazard ratio (HR) 2.49, 95% confidence interval (CI) 0.98–6.33,
p
= 0.056 and risk of death (HR 3.49, 95% CI 1.04–11.7,
p
= 0.042) compared with those who underwent LA.
Conclusions
Women in this study were less likely to receive adjuvant therapy if their nodal invasion was determined using SNB+LA compared with LA. These results suggest a lack of therapeutic measures available when a negative result is obtained by SNB+LA, which may have an impact on the risk of recurrence and survival.
Metastasis is a crucial step of malignant progression and is the primary cause of death from endometrial cancer. However, clinicians presently face the challenge that conventional ...surgical‐pathological variables, such as tumour size, depth of myometrial invasion, histological grade, lymphovascular space invasion or radiological imaging are unable to predict with accuracy if the primary tumour has metastasized. In the current retrospective study, we have used primary tumour samples of endometrial cancer patients diagnosed with (n = 16) and without (n = 27) lymph node metastasis to identify potential discriminators. Using peptide matrix assisted laser desorption/ionisation mass spectrometry imaging (MALDI‐MSI), we have identified m/z values which can classify 88% of all tumours correctly. The top discriminative m/z values were identified using a combination of in situ sequencing and LC‐MS/MS from digested tumour samples. Two of the proteins identified, plectin and α‐Actin‐2, were used for validation studies using LC‐MS/MS data independent analysis (DIA) and immunohistochemistry. In summary, MALDI‐MSI has the potential to identify discriminators of metastasis using primary tumour samples.
Lymph node metastasis is one of the most important indicators in breast cancer diagnosis, that is traditionally observed under the microscope by pathologists. In recent years, with the dramatic ...advance of high-throughput scanning and deep learning technology, automatic analysis of histology from whole-slide images has received a wealth of interest in the field of medical image computing, which aims to alleviate pathologists' workload and simultaneously reduce misdiagnosis rate. However, the automatic detection of lymph node metastases from whole-slide images remains a key challenge because such images are typically very large, where they can often be multiple gigabytes in size. Also, the presence of hard mimics may result in a large number of false positives. In this paper, we propose a novel method with anchor layers for model conversion, which not only leverages the efficiency of fully convolutional architectures to meet the speed requirement in clinical practice but also densely scans the whole-slide image to achieve accurate predictions on both micro- and macro-metastases. Incorporating the strategies of asynchronous sample prefetching and hard negative mining, the network can be effectively trained. The efficacy of our method is corroborated on the benchmark dataset of 2016 Camelyon Grand Challenge. Our method achieved significant improvements in comparison with the state-of-the-art methods on tumor localization accuracy with a much faster speed and even surpassed human performance on both challenge tasks.
To develop a clinical model for predicting high axillary nodal burden in patients with early breast cancer by integrating ultrasound (US) and clinicopathological features.
Patients with breast cancer ...who underwent preoperative US examination and breast surgery at the Affiliated Hospital of Nantong University (centre 1, n = 250) and at the Affiliated Hospital of Jiangsu University (centre 2, n = 97) between January 2012 and December 2016 and between January 2020 and March 2022, respectively, were deemed eligible for this study (n = 347). According to the number of lymph node (LN) metastasis based on pathology, patients were divided into two groups: limited nodal burden (0-2 metastatic LNs) and heavy nodal burden (≥ 3 metastatic LNs). In addition, US features combined with clinicopathological variables were compared between these two groups. Univariate and multivariate logistic regression analysis were conducted to identify the most valuable variables for predicting ≥ 3 LNs in breast cancer. A nomogram was then developed based on these independent factors.
Univariate logistic regression analysis revealed that the cortical thickness (p < 0.001), longitudinal to transverse ratio (p = 0.001), absence of hilum (p < 0.001), T stage (p = 0.002) and Ki-67 (p = 0.039) were significantly associated with heavy nodal burden. In the multivariate logistic regression analysis, cortical thickness (p = 0.001), absence of hilum (p = 0.042) and T stage (p = 0.012) were considered independent predictors of high-burden node. The area under curve (AUC) of the nomogram was 0.749.
Our model based on US variables and clinicopathological characteristics demonstrates that can help select patients with ≥ 3 LNs, which can in turn be helpful to predict high axillary nodal burden in early breast cancer patients and prevent unnecessary axillary lymph node dissection.
The aim of this study is to investigate whether the primary tumour response to neoadjuvant chemotherapy (NAC), based on the increase in the ADC-values (apparent diffusion coefficient) within the ...breast lesion, could help to predict axillary complete response.
We retrospectively included 74 patients who were treated with NAC followed by surgery at Lucus Augusti Hospital between January 2015 and September 2020. Simple logistic regression was used to evaluate the factors associated with axillary pathological complete response, including the changes in breast tumour ADC-values due to the treatment.
Axillary complete response was correlated with negative oestrogen receptor status, Her2 positivity and response of primary tumour. It was achieved in 31% of the patients. In addition, the increase in the tumour ADC-values with NAC was higher for responders. Among the tumours that demonstrated an increase in ADC-value >0.92 ×10
mm
/s, 42.8% (15/35) showed axillary complete response. Eight (20.5%) breast cancers with an increase in ADC below the cut-off value were found to have no metastatic nodes after treatment (
= 0.038).
Our results suggest that the performance of models predicting axillary response to NAC can be improved by adding the tumour response determined also using diffusion-weighted imaging.
For the fist time, we investigate the relation between tumour response to NAC, assessed using diffusion-weighted imaging, and axillary pathologic complete response.
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