Optical molecular imaging can differentiate metastatic from benign lymph nodes in head and neck cancer.
Ontology highlight
ABSTRACT:
SUBMITTER: Nishio N
PROVIDER: S-EPMC6834597 | biostudies-literature | 2019 Nov
REPOSITORIES: biostudies-literature
Publications
Optical molecular imaging can differentiate metastatic from benign lymph nodes in head and neck cancer.
Nishio Naoki N van den Berg Nynke S NS van Keulen Stan S Martin Brock A BA Fakurnejad Shayan S Teraphongphom Nutte N Chirita Stefania U SU Oberhelman Nicholas J NJ Lu Guolan G Horton Crista E CE Kaplan Michael J MJ Divi Vasu V Colevas A Dimitrios AD Rosenthal Eben L EL
Nature communications 20191106 1
Identification of lymph node (LN) metastasis is essential for staging of solid tumors, and as a result, surgeons focus on harvesting significant numbers of LNs during ablative procedures for pathological evaluation. Isolating those LNs most likely to harbor metastatic disease can allow for a more rigorous evaluation of fewer LNs. Here we evaluate the impact of a systemically injected, near-infrared fluorescently-labeled, tumor-targeting contrast agent, panitumumab-IRDye800CW, to facilitate the i ...[more]
Similar Datasets
Project description:Loco-regional control (LRC) is a major clinical endpoint after definitive radiochemotherapy (RCT) of head and neck cancer (HNC). Radiomics has been shown a promising biomarker in cancer research, however closer related to primary tumor control than composite endpoints. Radiomics studies often focus on the analysis of primary tumor (PT). We hypothesize that the combination of PT and lymph nodes (LN) radiomics better predicts LRC in HNC treated with RCT. Radiomics analysis was performed in CT images of 128 patients using Z-Rad implementation (training n?=?77, validation n?=?51). 285 features were extracted from PT and involved LN. Features were preselected with the maximum relevance minimum redundancy method and the multivariate Cox model was trained using least absolute shrinkage and selection operator. The mixed model was based on the combination of PT and LN radiomics, whereas the PT model included only the PT features. The mixed model showed significantly higher performance than the PT model (p?<?0.01), c-index of 0.67 and 0.63, respectively; and better risk group stratification. The clinical nodal status was not a significant predictor in the combination with PT radiomics. This study shows that the LRC can be better predicted by expansion of radiomics analysis with LN features.
| S-EPMC6811564 | biostudies-literature
Project description:BackgroundThe infiltrative nature and lymphatic metastasis of head and neck squamous cell carcinoma (HNSCC) are the main reasons leading to its poor prognosis.MethodsA multimodal surface-enhanced resonance Raman spectroscopy (SERRS) and magnetic resonance (MR) nanoprobe, in which paramagnetic chelators and heptamethine cyanine-based Raman reporter molecules were functionalized on a gold nanostar (AuS) surface was developed. Preoperative MRI and intraoperative SERRS-guided surgery were performed on rabbits bearing head and neck VX2 tumours to determine feasibility of the MR/SERRS probe in defining tumour marginal infiltration and lymph nodes metastasis.FindingsPreoperative T1-weighted MRI (T1W-MRI) unambiguously delineated the orthotopic head and neck VX2 tumour xenograft and detected the metastatic lymph nodes in rabbit models after intravenous administration of the probe. With the assistance of a hand-held Raman detector, the probe not only intra-operatively demarcated invasive tumour margins but also successfully distinguished metastatic lymph nodes via a remarkable attenuated Raman signal. Importantly, the group of rabbits subjected to the SERRS-guided surgery exhibited prolonged median survival time (78 days) compared with that of the control group without surgical intervention (29 days) or the group treated with conventional white-light-guided surgery (42 days) (P < 0.0001).Interpretationwe developed a novel AuS-based multimodal MR/SERRS probe. The capability of this probe to identify both a tumour xenograft and metastatic lymph nodes preoperatively by MRI and intra-operatively by SERRS not only avoids the need for unnecessary resection of neurological structures but also provides a new opportunity to improve the surgical prognosis of head and neck carcinoma of infiltrative nature.
| S-EPMC6921159 | biostudies-literature
Project description:Lymph node metastasis indicates poor prognosis in esophageal cancer. To understand the underlying mechanisms, most studies so far focused on investigating the tumors themselves and/or invaded lymph nodes. However they neglected the potential events within the metastatic niche, which precede invasion. Here we report the first description of these regulations in patients on transcription level. We determined transcriptomic profiles of still metastasis-free regional lymph nodes for two patient groups: patients classified as pN1 (n?=?9, metastatic nodes exist) or pN0 (n?=?5, no metastatic nodes exist). All investigated lymph nodes, also those from pN1 patients, were still metastasis-free. The results show that regional lymph nodes of pN1 patients differ decisively from those of pN0 patients--even before metastasis has taken place. In the pN0 group distinct immune response patterns were observed. In contrast, lymph nodes of the pN1 group exhibited a clear profile of reduced immune response and reduced proliferation, but increased apoptosis, enhanced hypoplasia and morphological conversion processes. DKK1 was the most significant gene associated with the molecular mechanisms taking place in lymph nodes of patients suffering from metastasis (pN1). We assume that the two molecular profiles observed constitute different stages of a progressive disease. Finally we suggest that DKK1 might play an important role within the mechanisms leading to lymph node metastasis.
| S-EPMC4105535 | biostudies-literature
Project description:Objectives18F-fluorodeoxyglucose (FDG) PET/CT has been widely used in tumor diagnosis, staging, and response evaluation. To determine an optimal therapeutic strategy for lung cancer patients, accurate staging is essential. Semi-quantitative standardized uptake value (SUV) is known to be affected by multiple factors and may fail to differentiate between benign and malignant lesions. Lymph nodes (LNs) in the mediastinal and pulmonary hilar regions with high FDG uptake due to granulomatous lesions such as tuberculosis, which has a high prevalence in China, pose a diagnostic challenge. This study aims to evaluate the diagnostic value of the quantitative metabolic parameters derived from dynamic 18F-FDG PET/CT in differentiating metastatic and non-metastatic LNs in lung cancer.MethodsOne hundred and eight patients with pulmonary nodules were enrolled to perform 18F-FDG PET/CT dynamic + static imaging with informed consent. One hundred and thirty-five LNs in 29 lung cancer patients were confirmed by pathology. Static image analysis parameters including LN-SUVmax, LN-SUVmax/primary tumor SUVmax (LN-SUVmax/PT-SUVmax), mediastinal blood pool SUVmax (MBP-SUVmax), LN-SUVmax/MBP-SUVmax, and LN-SUVmax/short diameter. Quantitative parameters including K1, k2, k3 and Ki and of each LN were obtained by applying the irreversible two-tissue compartment model using in-house Matlab software. Ki/K1 was computed subsequently as a separate marker. We further divided the LNs into mediastinal LNs (N=82) and pulmonary hilar LNs (N=53). Wilcoxon rank-sum test or Independent-samples T-test and receiver-operating characteristic (ROC) analysis was performed on each parameter to compare the diagnostic efficacy in differentiating lymph node metastases from inflammatory uptake. P<0.05 were considered statistically significant.ResultsAmong the 135 FDG-avid LNs confirmed by pathology, 49 LNs were non-metastatic, and 86 LNs were metastatic. LN-SUVmax, MBP-SUVmax, LN-SUVmax/MBP-SUVmax, and LN-SUVmax/short diameter couldn't well differentiate metastatic from non-metastatic LNs (P>0.05). However, LN-SUVmax/PT-SUVmax have good performance in the differential diagnosis of non-metastatic and metastatic LNs (P=0.039). Dynamic metabolic parameters in addition to k3, the parameters including K1, k2, Ki, and Ki/K1, on the other hand, have good performance in the differential diagnosis of metastatic and non-metastatic LNs (P=0.045, P=0.001, P=0.001, P=0.001, respectively). For ROC analysis, the metabolic parameters Ki (AUC of 0.672 [0.579-0.765], sensitivity 0.395, specificity 0.918) and Ki/K1 (AUC of 0.673 [0.580-0.767], sensitivity 0.570, specificity 0.776) have good performance in the differential diagnosis of metastatic from non-metastatic LNs than SUVmax (AUC of 0.596 [0.498-0.696], sensitivity 0.826, specificity 0.388), included the mediastinal region and pulmonary hilar region.ConclusionCompared with SUVmax, quantitative parameters such as K1, k2, Ki and Ki/K1 showed promising results for differentiation of metastatic and non-metastatic LNs with high uptake. The Ki and Ki/K1 had a high differential diagnostic value both in the mediastinal region and pulmonary hilar region.
| S-EPMC9686335 | biostudies-literature
Project description:Noninvasive localized measurement of extracellular pH in cancer tissues can have a significant impact on the management of cancer. Despite its significance, there are limited approaches for rapid and noninvasive measurement of local pH in a clinical environment. In this study, we demonstrate the potential of noninvasive topical delivery of Alexa-647 labeled pHLIP (pH responsive peptide conjugated with Alexa Fluor(®) 647) to image changes in extracellular pH associated with head and neck squamous cell carcinoma using widefield and high resolution imaging. We report a series of preclinical analyses to evaluate the optical contrast achieved after topical delivery of Alexa-647 labeled pHLIP in intact fresh human tissue specimens using widefield and high-resolution fluorescence imaging. Using topical delivery, Alexa-647 labeled pHLIP can be rapidly delivered throughout the epithelium of intact tissues with a depth exceeding 700 µm. Following labeling with Alexa-647 labeled pHLIP, the mean fluorescent contrast increased four to eight fold higher in clinically abnormal tissues as compared to paired clinically normal biopsies. Furthermore, the imaging approach showed significant differences in fluorescence contrast between the cancer and the normal biopsies across diverse patients and different anatomical sites (unpaired comparison). The fluorescence contrast differences between clinically abnormal and normal tissues were in agreement with the pathologic evaluation. Topical application of fluorescently labeled pHLIP can detect and differentiate normal from cancerous tissues using both widefield and high resolution imaging. This technology will provide an effective tool to assess tumor margins during surgery and improve detection and prognosis of head and neck cancer.
| S-EPMC4405778 | biostudies-literature
Project description:Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in adults. DLBCL exhibits highly aggressive and systemic progression into multiple tissues in patients, particularly in lymph nodes. Whole-body 18F-fluodeoxyglucose positron emission tomography ([18F]FDG-PET) imaging has an essential role in diagnosing DLBCL in the clinic; however, [18F]FDG-PET often faces difficulty in differentiating malignant tissues from certain nonmalignant tissues with high glucose uptake. We have developed a PET imaging strategy for DLBCL that targets poly[ADP ribose] polymerase 1 (PARP1), the expression of which has been found to be much higher in DLBCL than in healthy tissues. In a syngeneic DLBCL mouse model, this PARP1-targeted PET imaging approach allowed us to discriminate between malignant and inflamed lymph nodes, whereas [18F]FDG-PET failed to do so. Our PARP1-targeted PET imaging approach may be an attractive addition to the current PET imaging strategy to differentiate inflammation from malignancy in DLBCL.
| S-EPMC5594659 | biostudies-literature
Project description:Despite major advances in targeted drug therapy and radiation therapy, surgery remains the most effective treatment for most solid tumors. The single most important predictor of patient survival is a complete surgical resection of the primary tumor, draining lymph nodes, and metastatic lesions. Presently, however, 20%-30% of patients with head and neck cancer who undergo surgery still leave the operating room without complete resection because of missed lesions. Thus, major opportunities exist to develop advanced imaging tracers and intraoperative instrumentation that would allow surgeons to visualize microscopic tumors during surgery. The cell adhesion molecule integrin αvβ3 is specifically expressed by tumor neovasculature and invading tumor cells, but not by quiescent vessels or normal cells. Here we report the combined use of an integrin-targeting near-infrared tracer (RGD-IRDye800CW) and a handheld spectroscopic device, an integrated point spectroscopy with wide-field imaging system, for highly sensitive detection of integrin overexpression on infiltrating cancer cells. By using an orthotopic head and neck cancer animal model, we show that this tracer-device combination allows intraoperative detection of not only invasive tumor margins but also metastatic lymph nodes. Correlated histological analysis further reveals that microscopic clusters of 50-100 tumor cells can be detected intraoperatively with high sensitivity and specificity, raising new possibilities in guiding surgical resection of microscopic tumors and metastatic lymph nodes.
| S-EPMC5058361 | biostudies-literature
Project description:BackgroundMolecular diagnosis has been proposed to enhance the intra-operative diagnosis of sentinel lymph node (SLN) invasion in head and neck squamous cell carcinoma (HNSCC). Although cytokeratin (CK) mRNA quantification with real-time reverse transcriptase-PCR (QRT-PCR) has produced encouraging results, the more discriminating markers remain to be identified.MethodsPemphigus vulgaris antigen (PVA), squamous cell carcinoma antigen (SCCA), and CK17 mRNA were quantified using QRT-PCR, and the results were compared with an extensive histopathological examination of the entire SLNs on 78 SLNs harvested from 22 patients with HNSCC.ResultsSCCA and CK17 quantification showed significantly higher mRNA values for macrometastases (MAs) than for either negative or isolated tumour cell (ITC) SLNs (P<0.01). Pemphigus vulgaris antigen allowed the discrimination of all MAs and micrometastases from both negative and ITC SLNs (P<0.001). For the neck staging of patients, considering metastatic vs non-metastatic status, receiver-operating characteristic curve analysis found areas under the curve of 93.8, 97.9, and 100% for CK17, SCCA, and PVA, respectively. With PVA, a cutoff value of 562 copies per 100 ng of cDNA permitted the correct distinction between patients with positive as opposed to negative neck nodes in all cases.ConclusionPVA seems to be a highly promising marker for accurate intra-operative SLN staging in HNSCC by QRT-PCR.
| S-EPMC2813735 | biostudies-literature
Project description:OBJECTIVES/HYPOTHESIS:Clinical staging of early head and neck squamous cell carcinoma (SCCHN) is often inaccurate, leading to elective neck dissection to detect the 30% of patients with micrometastatic disease. Sentinel node biopsy accurately stages the regional lymphatics, but intraoperative pathology is only moderately sensitive, and final pathology takes several days to complete. To facilitate immediate neck dissection where necessary, we have identified several promising marker genes of SCCHN metastasis and developed a rapid, accurate, and automated quantitative real-time polymerase chain reaction (PCR) (qRT-PCR) assay for intraoperative use. STUDY DESIGN:Prospective tissue collection, retrospective pathologic correlation with qRT-PCR. METHODS:From a 40-gene marker screen, we quantified expression of 11 potential tumor genes using a test set of primary tumors (n = 32) and metastatic (n = 19) and benign (n = 10) lymph nodes. Eight patients' paired primary tumor and metastatic nodes were included. A validation set of 442 grossly tumor-negative nodes was evaluated for expression of the most promising markers, comparing metastasis detection by qRT-PCR with pathologic analysis (hematoxylin and eosin and immunohistochemistry). A novel multiplexed, automated, single-tube qRT-PCR assay was used to analyze more than 100 lymph nodes using a two-marker, 35-minute assay to determine its negative predictive value. RESULTS:Based on expression of 11 tumor-associated genes from the marker screen, the two most promising markers of SCCHN metastasis in the test set, pemphigus vulgaris antigen (PVA) and tumor-associated calcium signal transducer 1 (TACSTD1), also known as epithelial cell adhesion molecule (EpCAM), were selected. Development of a multiplexed qRT-PCR assay for the detection of metastasis compared favorably with pathologic analysis in the additional 442-node set. A rapid, multiplexed assay using PVA and TACSTD1 demonstrated excellent reproducibility, linearity, and accuracy (?96% negative predictive value) for identifying positive (n = 40) and negative (n = 62) nodes in a validation subset. CONCLUSIONS:Detection of metastatic SCCHN using multiplexed qRT-PCR can be rapid, accurate, and automated and may enable sentinel node biopsy to be used for intraoperative decision-making. PCR amplification of tumor marker genes is an effective method of intraoperative molecular staging of SCCHN and could more appropriately guide application of neck dissection in pN+ SCCHN patients, sparing 60% to 70% of pN0 patients from unnecessary neck dissection. This technique may also be used for identifying residual neck disease posttreatment, using outpatient fine-needle aspiration biopsy specimens.
| S-EPMC3418874 | biostudies-literature
Project description:Aim: The purpose of this study was to assess the ability of contrast-enhanced ultrasonography (CEUS) in the differential diagnosis of cancerous lymph nodes. Methods: Contrast-enhanced ultrasonography was performed in the cervical nodules of included patients, and the diagnoses were confirmed by pathological examination. Contrast-enhanced ultrasonography images and parameters of head and neck lymphomas were compared with those of cancerous lymph nodes. Besides, receiver operating characteristic curve was operated to access the diagnostic value of CEUS. Results: Finally, a total of 63 head and neck lymphomas and 80 cervical cancerous lymph nodes were enrolled in this study. Results showed that the CEUS images of lymphoma were mainly characterized by homogeneous enhancement (71.43%), and approximately half of them were centripetal perfusion (58.73%), whereas most CEUS images of cancerous lymph nodes were inhomogeneous enhancement (82.50%) and centripetal perfusion (92.50%). Quantitative analysis of CEUS parameters indicated that PI (derived peak intensity) and AUC (area under the curve) of lymphomas were both lower than those of cancerous lymph nodes (PI: 8.78 vs. 10.51, AUC: 652.62 vs. 784.09, respectively) (P < 0.05). Receiver operating characteristic analysis showed that the sensitivity of CEUS parameters in the differential diagnosis was significant (80.00%), although the specificity was not high (47.62%). When parameters were combined with the image features, the accuracy of diagnosis was greatly improved (from 0.655 to 0.899). Conclusion: Contrast-enhanced ultrasonography could be a promising tool for the differential diagnosis of head and neck lymphomas and cancerous lymph nodes.
| S-EPMC7186353 | biostudies-literature