Node Target Research Articles

Abstract PO5-23-02: Targeted Axillary Dissection with Paramagnetic Marker Localization

Abstract Background: Targeted axillary dissection (TAD), the combination of sentinel lymph node biopsy (SLNB) and targeted lymph node biopsy (TLNB), can reduce the false negative rates of SLNB alone dramatically in breast cancer patients, who received neoadjuvant chemotherapy (NACT). However optimal methods for TAD are still under investigation. A paramagnetic marker Magseed® was used for the identification of the TLN in this study. Methods: 80 patients eligible to receive NACT were included. All patients had positive axillary lymph nodes verified by core biopsy. Six patients did not receive NACT for any reason. After NACT the targeted lymph nodes (TLNs) were marked with Magseed®, a non-radioactive paramagnetic marker. The SLNs were marked with dual tracer method. The SLNB and the selective TLNB were performed in 74 patients. The Magseed® marked TLNs were identified with the Sentimag® probe and excised. Specimen x-ray was performed to confirm the Magseed® within the prior to NACT biopsied and clipped lymph node. The identification rates of TLNs and SLNs, and the concordance rates were calculated. Results: The TLN identification rate was 100% (74/74), the SLN identification rate was 81.1% (60/74), the concordance rate of TLN and SLN was 58.1% (43/74). In 66.2% (49/74) of the patients the TLN converted to negative, and no ALND was performed. When the TLN converted to negative, a SLN could not be identified in 18.4% (9/49) of the patients. In 33.8% (25/74) of the patients the TLN remained positive after NACT and ALND was performed. When the TLN remained positive, a SLN could not be identified in 40% (10/25) of the patients. Complications according Magseed® deployment or identification could not be observed. Conclusion: Magseed® is a reliable and feasible marker for the identification of TLNs after NACT. Citation Format: Roland Reitsamer, Andreas Sir, Ernst Forsthuber, Florentia Peintinger. Targeted Axillary Dissection with Paramagnetic Marker Localization [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-23-02.

Abstract PO4-19-04: AXSANA – EUBREAST-3: An international prospective multicenter cohort study to evaluate different surgical methods of axillary staging in clinically node-positive breast cancer patients treated with neoadjuvant chemotherapy

Abstract Background The optimal surgical staging procedure of the axilla in patients who convert from a clinically positive (cN+) to a clinically negative node status (ycN0) through neoadjuvant chemotherapy is still controversial. Widely diverse techniques such as full Axillary Lymph Node Dissection (ALND), Targeted Axillary Dissection (TAD), Targeted Lymph Node Biopsy (TLNB) and Sentinel Lymph Node Biopsy (SLNB) alone are given preference in different international guidelines. So far, no comparative data on the oncological outcome or the morbidity of the different procedures are available. Further research is needed to safely de-escalate the extent of axillary surgery in this patient group. Trial design The AXSANA study is an international prospective cohort study including cN+ patients converting to ycN0 status and treated with different axillary staging techniques according to the standard at their treating institution. The study was initiated by the EUBREAST network. The trial includes patients with cT1-4c tumors, who present initially with axillary lymph node metastasis scheduled for neoadjuvant chemotherapy. According to an amendment in 2020 the inclusion of patients with highly suspicious nodes without confirmation using a minimally invasive biopsy is allowed. All patients converting to ycN0 status undergo follow-up for 5 years irrespectively of the ypN status. Primary endpoints: Invasive disease-free survival, axillary recurrence rate and health-related quality of life (HRQoL). HRQoL are evaluated using four standardized questionnaires (EORTC QLQ-C 30, EORTC QLQ-BR 23, Lymph ICF and SOC-13) at baseline and after 1, 3 and 5 years after surgery. Secondary endpoints are the feasibility and performance of different axillary staging techniques (detection rate, number of removed lymph nodes and association with complications, arm morbidity and quality of life, operating time and use of clinical and economic resources); impact of learning curve, and the detailed mapping of surgical and oncological treatment standards in different countries. The impact on different regional treatment strategies (radiotherapy, ALND) in patients with ypN0(i+), ypN1(mi) and ypN1 is assessed. Current status of the study: 4336 patients from 284 study sites and 26 countries were enrolled in the study between June 2020 and June 2023. Among 3722 patients with a defined surgical concept 1631 women were scheduled for TAD, 1483 for ALND, 469 for SLNB, 25 for TLNB and 109 for other procedures. A target lymph node was marked in 2309 patients, most frequently using clips/coils (1850, 80.1%), followed by magnetic seeds (219, 9.5%), carbon ink (171, 7.4%), radar marker (80, 3.5%), radioactive seeds (4, 0.2%) and other techniques (24, 1.0%). Funding: AGO-B, GBG, Claudia-von Schilling Foundation, Ehmann Foundation, Eugen und Irmgard Hahn Foundation, AWOgyn, Merit Medical, Endomagnetics, Mammotome Contact information: Prof. Dr. Thorsten Kühn Department of Gynecology and Obstetrics University of Ulm, Germany Baumreute 37 D-73730 Esslingen Germany E-Mail: kuehn.thorsten@t-online.de Citation Format: Thorsten Kühn, Steffi Hartmann, Elmar Stickeler, Jana de Boniface, Oreste Davide Gentilini, Sarah Fröhlich, Franziska Ruf, Marc Thill, Michael Hauptmann, Guldeniz Karadeniz Cakmak, Isabel Rubio, Maria Luisa Gasparri, Michalis Kontos, Eduard-Alexandru Bonci, Laura Niinikoski, Bilge Aktas Sezen, Rosa Di Micco, Dawid Murawa, Geeta Kadayaprath, David Pinto, Florentia Peintinger, Matilda Appelgren, Janine M. Simons, Marjolein Smidt, Ellen Schlichting, Lukas Dostalek, Elisabeth Thiemann, Markus Hahn, Michael Schrauder, Semra Gunay, Gunay Gurleyik, Nina Helidon, Hagigat Valiyeva, Ashutosh Kothari, Marian Vanhoeij, Andraz Perhavec, Tsvetomir Ivanov, Dov Zippel, Lia Rebaza, Sarun Thongvitokomarn, Sibylle Loibl, Maggie Banys-Paluchowski. AXSANA – EUBREAST-3: An international prospective multicenter cohort study to evaluate different surgical methods of axillary staging in clinically node-positive breast cancer patients treated with neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-19-04.

Abstract PO1-01-07: Cryoablation and endocrine therapy for clinical stage I/II, ER+ breast cancer in patients with omission of surgical axillary staging. A retrospective study

Abstract OBJECTIVE To evaluate the efficacy of combined treatment with ultrasound-guided cryoablation and endocrine therapy (ET) in hormone receptor-positive (ER+), HER2-negative (HER-) invasive breast cancer (BC) patients with clinical stage I/II who are not candidates for axillary surgery. PATIENTS AND METHODS Patients with ER+, HER- invasive BC in clinical stage I/II who did not undergo sentinel lymph node biopsy (SLNB) or target axillary dissection (TAD) were included. They received treatment consisting of ultrasound-guided cryoablation combined with daily letrozole 2.5 mg orally. Cryoablation was performed as the initial treatment for BC < 15mm, followed by adjuvant ET, while neoadjuvant ET was administered for 6-12 months before cryoablation for BC ≥ 15mm. Cryoablation was performed using the ICEfx Galil argon gas system (Boston Scientific, USA) and the ProSense liquid nitrogen system (IceCure Medical Ltd, Caesarea, Israel). Follow-up breast ultrasound examinations were conducted every six months. Patients with a minimum follow-up of 12 months after cryoablation were included in the study. Core needle biopsies were performed if recurrence was suspected, and rescue cryoablation was considered for confirmed relapse. The tolerance and safety of the procedures were recorded. RESULTS From March 2019 to July 2023, a total of 96 patients with 105 ER+, HER2- invasive BC in clinical stage I/II who did not undergo SLNB or TAD were treated with ultrasound-guided cryoablation and ET. Among them, 58 patients (aged 58-96 years, mean 83, SD ±7.64) with 64 BC lesions (ranging from 5 to 60mm, mean 17, SD ±13.75) were followed up for a minimum of 12 months, with a mean follow-up period of 24 months (ranging from 12 to 50 months). The invasive carcinomas included 40 ductal, 16 lobular, 5 colloid, and 3 papillary cases. The ipsilateral breast tumor recurrence rate was 1,72% (1/58 patients). One patient with lobular carcinoma experienced a relapse at 17 months. Rescue cryoablation was performed, and after 25 months, she remains free of recurrence. Therefore, local control was achieved in all patients. Six patients died from causes unrelated to BC during the follow-up period. All procedures were well-tolerated with local anesthesia, and no serious complications were reported. CONCLUSION Ultrasound-guided cryoablation with ET constitutes an effective combined treatment for the local control of ER+, HER2- BC in patients with clinical stage I/II and omission for surgical axillary staging. Cryoablation is a very well tolerated procedure without morbidity. Citation Format: José María Oliver Goldaracena, Pilar Zamora, Covadonga Marti, Vicenta Córdoba Chicote, Maria José Roca Navarro, Diego Garrido Alonso, Ylenia Navarro Monforte, Teresa Diaz de Bustamante Durban, Fernando García Martínez, Jose Ignacio Sanchez-Mendez, Elisa York Pineda, Laura Yebenes Gregorio, Adolfo Loayza, Laura Frías Aldeguer, Elisa Moreno Palacios, Marcos Melendez Gisper, Joaquin Gomez Ramirez, Luis Asensio Gómez, Virginia Martínez Marín, David Hardisson Hernáez, Alberto Berjón García. Cryoablation and endocrine therapy for clinical stage I/II, ER+ breast cancer in patients with omission of surgical axillary staging. A retrospective study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-01-07.

Axillary Surgery for Breast Cancer in 2024.

Axillary surgery for patients with breast cancer (BC) in 2024 is becoming increasingly specific, moving away from the previous 'one size fits all' radical approach. The goal is to spare morbidity whilst maintaining oncologic safety. In the upfront surgery setting, a first landmark randomized controlled trial (RCT) on the omission of any surgical axillary staging in patients with unremarkable clinical examination and axillary ultrasound showed non-inferiority to sentinel lymph node (SLN) biopsy (SLNB). The study population consisted of 87.8% postmenopausal patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative BC. Patients with clinically node-negative breast cancer and up to two positive SLNs can safely be spared axillary dissection (ALND) even in the context of mastectomy or extranodal extension. In patients enrolled in the TAXIS trial, adjuvant systemic treatment was shown to be similar with or without ALND despite the loss of staging information. After neoadjuvant chemotherapy (NACT), targeted lymph node removal with or without SLNB showed a lower false-negative rate to determine nodal pathological complete response (pCR) compared to SLNB alone. However, oncologic outcomes do not appear to differ in patients with nodal pCR determined by either one of the two concepts, according to a recently published global, retrospective, real-world study. Real-world studies generally have a lower level of evidence than RCTs, but they are feasible quickly and with a large sample size. Another global real-world study provides evidence that even patients with residual isolated tumor cells can be safely spared from ALND. In general, few indications for ALND remain. Three randomized controlled trials are ongoing for patients with clinically node-positive BC in the upfront surgery setting and residual disease after NACT. Pending the results of these trials, ALND remains indicated in these patients.

Lymph node targeting strategy using a hydrogel sustained-release system to load effector memory T cells improves the anti-tumor efficacy of anti-PD-1

Communication between tumors and lymph nodes carries substantial significance for antitumor immunotherapy. Remodeling the immune microenvironment of tumor-draining lymph nodes (TdLN) plays a key role in enhancing the anti-tumor ability of immunotherapy. In this study, we constructed a biomimetic artificial lymph node structure composed of F127 hydrogel loading effector memory T (TEM) cells and PD-1 inhibitors (aPD-1). The biomimetic lymph nodes facilitate the delivery of TEM cells and aPD-1 to the TdLN and the tumor immune microenvironment, thus realizing effective and sustained anti-tumor immunotherapy. Exploiting their unique gel-forming and degradation properties, the cold tumors were speedily transformed into hot tumors via TEM cell supplementation. Meanwhile, the efficacy of aPD-1 was markedly elevated compared with conventional drug delivery methods. Our finding suggested that the development of F127@TEM@aPD-1 holds promising potential as a future novel clinical drug delivery technique. Statement of significanceF127@TEM@aPD-1 show unique advantages in cancer treatment. When injected subcutaneously, F127@TEM@aPD-1 can continuously supplement TEM cells and aPD-1 to tumor draining lymph nodes (TdLN) and the tumor microenvironment, not only improving the efficacy of ICB therapy through slow release, but also exhibiting dual regulatory effects on the tumor and TdLN.

A Manganese-Based Nanodriver Coordinates Tumor Prevention and Suppression through STING Activation in Glioblastoma.

Glioblastoma (GBM), the most prevalent and aggressive primary malignant brain tumor, exhibits profound immunosuppression and demonstrates a low response rate to current immunotherapy strategies. Manganese cations (Mn2+) directly activate the cGAS/STING pathway and induce the unique catalytic synthesis of 2'3'-cGAMP to facilitate type I IFN production, thereby enhancing innate immunity. Here, a telodendrimer and Mn2+-based nanodriver (PLHM) with a small size is developed, which effectively target lymph nodes through the blood circulation and exhibit tumor-preventive effects at low doses of Mn2+ (3.7mg kg-1). On the other hand, the PLHM nanodriver also exhibits apparent antitumor effects in GBM-bearing mice via inducing in vivo innate immune responses. The combination of PLHM with doxorubicin nanoparticles (PLHM-DOX NPs) results in superior inhibition of tumor growth in GBM-bearing mice due to the synergistic potentiation of STING pathway functionality by Mn2+ and the presence of cytoplasmic DNA. These findings demonstrate that PLHM-DOX NPs effectively stimulate innate immunity, promote dendritic cell maturation, and orchestrate cascaded infiltration of CD8 cytotoxic T lymphocytes within glioblastomas characterized by low immunogenicity. These nanodivers chelated with Mn2+ show promising potential for tumor prevention and antitumor effects on glioblastoma by activating the STING pathway.

Lymph Node Targeting Mediated by Albumin Hitchhiking of Synthetic Tn Glycolipid Leads to Robust In Vivo Antibody Production.

Tn antigen is a tumor-associated carbohydrate antigen, which is present prominently on the tumor cell surfaces and attracts an interest in vaccine development. This work demonstrates that a synthetic Tn antigen carrying glycoconjugate forms a complex with circulating albumin, delivers the antigen to lymph nodes (LNs), and leads to the efficient production of antibodies against the antigen. Synthetic Tn antigen glycoconjugate, possessing DSPE-PEG2000 linker and lipophilic moieties, undergoes micellization in PBS buffer. In the presence of bovine serum albumin (BSA), demicellization of the glycolipid occurs, with a rate constant of 0.18 min-1. In vitro studies show that the glycoconjugate binds preferentially to BSA in the presence of cells. Immunological assessments in mice models reveal the albumin-enabled delivery of the Tn glycoconjugate to antigen-presenting cells in the LNs, specifically leading to a robust humoral immune response. ELISA titers show superior binding, with a saturation dilution of 1:51 200 for Tn glycoconjugate, in comparison to that mediated by the Tn-BSA covalent conjugate with a saturation dilution of 1:6400. Immunohistochemical staining shows delivery of Tn glycoconjugate at the LNs, specifically at the subcapsular sinus and interfollicular areas. The work highlights the potential of albumin-mediated target delivery strategy for cancer immunotherapies.

Dual-energy computed tomography in a multiparametric regression model for diagnosing lymph node metastases in pancreatic ductal adenocarcinoma

ObjectiveTo investigate the diagnostic value of dual-energy computed tomography (DECT) quantitative parameters in the identification of regional lymph node metastasis in pancreatic ductal adenocarcinoma (PDAC).MethodsThis retrospective diagnostic study assessed 145 patients with pathologically confirmed pancreatic ductal adenocarcinoma from August 2016–October 2020. Quantitative parameters for targeted lymph nodes were measured using DECT, and all parameters were compared between benign and metastatic lymph nodes to determine their diagnostic value. A logistic regression model was constructed; the receiver operator characteristics curve was plotted; the area under the curve (AUC) was calculated to evaluate the diagnostic efficacy of each energy DECT parameter; and the DeLong test was used to compare AUC differences. Model evaluation was used for correlation analysis of each DECT parameter.ResultsStatistical differences in benign and metastatic lymph nodes were found for several parameters. Venous phase iodine density had the highest diagnostic efficacy as a single parameter, with AUC 0.949 [95% confidence interval (CI):0.915–0.972, threshold: 3.95], sensitivity 79.80%, specificity 96.00%, and accuracy 87.44%. Regression models with multiple parameters had the highest diagnostic efficacy, with AUC 0.992 (95% CI: 0.967–0.999), sensitivity 95.96%, specificity 96%, and accuracy 94.97%, which was higher than that for a single DECT parameter, and the difference was statistically significant.ConclusionAmong all DECT parameters for regional lymph node metastasis in PDAC, venous phase iodine density has the highest diagnostic efficacy as a single parameter, which is convenient for use in clinical settings, whereas a multiparametric regression model has higher diagnostic value compared with the single-parameter model.

Endobronchial ultrasound-transbronchial needle aspiration: effectiveness and accuracy in non-small cell lung cancer staging.

Endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) has a cardinal role in the diagnosis and staging of non-small cell lung cancer (NSCLC), providing an accurate nodal staging in a less invasive way than surgical biopsy. The aim of this study was to assess the diagnostic accuracy of EBUS-TBNA in the pre-operative NSCLC mediastinal staging, as well as to evaluate EBUS-TBNA specificity and sensibility in our cohort. We retrospectively analyzed data of NSCLC patients who underwent EBUS-TBNA followed by major pulmonary resection between January 2020 and December 2022. EBUS-TBNA was performed in patients with NSCLC (central T ≤ 3cm, peripheral/central T > 3cm), following the ESTS guidelines. The target nodes were selected on the basis of their radiologic/metabolic characteristics. Each procedure was conducted together with rapid on-site cytological evaluation (ROSE). Twenty-five patients were included (M/F = 17/8). At least three needle passages on each target lymph node were performed. No complications during or after the procedures occurred. We found a 100% correspondence between ROSE on the sampled nodes and postoperative pathologic findings. An upstaging occurred in three cases (12%) because of the involvement of stations 5 and 6 (not accessible via EBUS), while the only case of downstaging (N2 → N0, 4%) was probably due to intercurrent neoadjuvant chemotherapy. In all cases, EBUS-TBNA has proved to achieve a diagnostic procedure on the target nodes. EBUS-TBNA is a safe and effective procedure that offers high sensitivity and specificity when performed together with ROSE, which improves the accuracy of sampling. Doubt on nodal stations 5 and 6 involvement should be settled by other techniques.

Biologically Self-Assembled Tumor Cell-Derived Cancer Nanovaccines as an All-in-One Platform for Cancer Immunotherapy.

Tumor cell-derived cancer nanovaccines introduce tumor cell-derived components as functional units that endow the nanovaccine systems with some advantages, especially providing all potential tumor antigens. However, cumbersome assembly steps, potential risks of exogenous adjuvants, as well as insufficient lymph node (LN) targeting and dendritic cell (DC) internalization limit the efficacy and clinical translation of existing tumor cell-derived cancer nanovaccines. Herein, we introduced an endoplasmic reticulum (ER) stress inducer α-mangostin (αM) into tumor cells through poly(d, l-lactide-co-glycolide) nanoparticles and harvested biologically self-assembled tumor cell-derived cancer nanovaccines (αM-Exos) based on the biological process of tumor cell exocytosing nanoparticles through tumor-derived exosomes (TEXs). Besides presenting multiple potential antigens, αM-Exos inherited abundant 70 kDa heat shock proteins (Hsp70s) upregulated by ER stress, which can not only act as endogenous adjuvants but also improve LN targeting and DC internalization. Following subcutaneous injection, αM-Exos efficiently migrated to LNs and was expeditiously endocytosed by DCs, delivering tumor antigens and adjuvants to DCs synchronously, which then powerfully triggered antitumor immune responses and established long-term immune memory. Our study exhibited an all-in-one biologically self-assembled tumor cell-derived cancer nanovaccine platform, and the fully featured cancer nanovaccines assembled efficiently through this platform are promising for desirable cancer immunotherapy.

Quantitative evaluation of endobronchial ultrasound elastography in the diagnosis of benign and malignant mediastinal and hilar lymph nodes

ObjectiveTo compare the diagnostic value of different quantitative methods of endobronchial ultrasound elastography in benign and malignant mediastinal and hilar lymph nodes. MethodsThis retrospective study included patients who underwent endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for mediastinal and hilar lymph node enlargement in our hospital between January 2019 and August 2022. We compared different quantitative elastography parameters [red area ratio (RAR, lymph node red area/lymph node area), green area ratio (GAR, lymph node green area/lymph node area), blue area ratio (SAR, lymph node blue area/lymph node area), mixed area ratio (MAR, lymph node green area/lymph node area), blue-green lymph node area/lymph node area), strain rate ratio (SR), strain rate in the target lymph node (LPA), ratio of blue area to total lymph node area outside the center of the target lymph node (PAR), and average grey value (MGV)], in order to find the best quantitative evaluation method. ResultsA total of 244 patients (346 lymph nodes) were included in this study. All quantitative elastography parameters were statistically significant for the differentiation of benign and malignant lesions except the average grey value of the target lymph nodes. The area under the receiver operating characteristic curve of SAR was 0.872 (95% confidence interval: 0.83−0.91), the cutoff value was 0.409, and the sensitivity, specificity, positive and negative predictive values were 85.4%, 78.0%, 80.4%, and 83.4%, respectively. ConclusionCompared with other types of quantitative analysis, SAR has a higher predictive significance for benign and malignant lymph nodes.

Lymph Node-Targeted Vaccine Boosting of TCR T-cell Therapy Enhances Antitumor Function and Eradicates Solid Tumors.

T-cell receptor (TCR)-modified T-cell therapies have shown promise against solid tumors, but overall therapeutic benefits have been modest due in part to suboptimal T-cell persistence and activation in vivo, alongside potential tumor antigen escape. In this study, we demonstrate an approach to enhance the in vivo persistence and function of TCR T cells through combination with Amphiphile (AMP) vaccination including cognate TCR T peptides. AMP modification improves lymph node targeting of conjugated tumor immunogens and adjuvants, thereby coordinating a robust T cell-activating endogenous immune response. AMP vaccine combination with TCR T-cell therapy led to complete eradication and durable responses against established murine solid tumors refractory to TCR T-cell monotherapy. Enhanced antitumor efficacy was correlated with simultaneous in vivo invigoration of adoptively transferred TCR T cells and in situ expansion of the endogenous antitumor T-cell repertoire. Long-term protection against tumor recurrence in AMP-vaccinated mice was associated with antigen spreading to additional tumor-associated antigens not targeted by vaccination. AMP vaccination further correlated with pro-inflammatory lymph node transcriptional reprogramming and increased antigen presenting-cell maturation, resulting in TCR T-cell expansion and functional enhancement in lymph nodes and solid tumor parenchyma without lymphodepletion. In vitro evaluation of AMP peptides with matched human TCR T cells targeting NY-ESO-1, mutant KRAS, and HPV16 E7 illustrated the clinical potential of AMP vaccination to enhance human TCR T-cell proliferation, activation, and antitumor activity. Taken together, these studies provide rationale and evidence to support clinical evaluation of combining AMP vaccination with TCR T-cell therapies to augment antitumor activity.

Coefficient of Variation in Metastatic Lymph Nodes Determined by 18F-FDG PET/CT in Patients with Advanced NSCLC: Combination with Coefficient of Variation in Primary Tumors.

Purpose The aim of the present study was to test whether the coefficient of variation (CoV) of 18F-FDG PET/CT images of metastatic lymph nodes and primary tumors may predict clinical outcome in patients with advanced non-small cell lung cancer (NSCLC). Materials and Methods Fifty-eight NSCLC patients who had undergone 18F-FDG PET/CT at diagnosis were evaluated. SUVmax, SUVmean, CoV, MTV and TLG were determined in targeted lymph nodes and corresponding primary tumors along with Total MTV (MTVTOT) and Whole-Body TLG (TLGWB) of all malignant lesions. Univariate analysis was performed using Cox proportional hazards regression whereas the Kaplan-Meier method and log-rank tests were used for survival analysis. Results Fifty-eight metastatic lymph nodes were analyzed and average values of SUVmax, SUVmean, CoV, MTV and TLG were 11.89 ± 8.54, 4.85 ± 1.90, 0.37 ± 0.16, 46.16 ± 99.59 mL and 256.84 ± 548.27 g, respectively, whereas in primary tumors they were 11.92 ± 6.21, 5.47 ± 2.34, 0.36 ± 0.14, 48.03 ± 64.45 mL and 285.21 ± 397.95 g, respectively. At univariate analysis, overall survival (OS) was predicted by SUVmax (p = 0.0363), SUVmean (p = 0.0200) and CoV (p = 0.0139) of targeted lymph nodes as well as by CoV of primary tumors (p = 0.0173), MTVTOT (p = 0.0007), TLGWB (p = 0.0129) and stage (p = 0.0122). Using Kaplan-Meier analysis, OS was significantly better in patients with CoV of targeted lymph nodes ≤ 0.29 than those with CoV > 0.29 (p = 0.0147), meanwhile patients with CoV of primary tumors > 0.38 had a better prognosis compared to those with CoV ≤ 0.38 (p = 0.0137). Finally, we combined the CoV values of targeted lymph nodes and primary tumors in all possible arrangements and a statistically significant difference was found among the four survival curves (p = 0.0133). In particular, patients with CoV of targeted lymph nodes ≤ 0.29 and CoV of primary tumors > 0.38 had the best prognosis. Conclusions The CoV of targeted lymph nodes combined with the CoV of primary tumors can predict prognosis of NSCLC patients.

A facile approach to preparing personalized cancer vaccines using iron-based metal organic framework.

Considering the diversity of tumors, it is of great significance to develop a simple, effective, and low-cost method to prepare personalized cancer vaccines. In this study, a facile one-pot synthetic route was developed to prepare cancer vaccines using model antigen or autologous tumor antigens based on the coordination interaction between Fe3+ ions and endogenous fumarate ligands. Herein, Fe-based metal organic framework can effectively encapsulate tumor antigens with high loading efficiency more than 80%, and act as both delivery system and adjuvants for tumor antigens. By adjusting the synthesis parameters, the obtained cancer vaccines are easily tailored from microscale rod-like morphology with lengths of about 0.8 μm (OVA-ML) to nanoscale morphology with sizes of about 50~80 nm (OVA-MS). When cocultured with antigen-presenting cells, nanoscale cancer vaccines more effectively enhance antigen uptake and Th1 cytokine secretion than microscale ones. Nanoscale cancer vaccines (OVA-MS, dLLC-MS) more effectively enhance lymph node targeting and cross-presentation of tumor antigens, mount antitumor immunity, and inhibit the growth of established tumor in tumor-bearing mice, compared with microscale cancer vaccines (OVA-ML, dLLC-ML) and free tumor antigens. Our work paves the ways for a facile, rapid, and low-cost preparation approach for personalized cancer vaccines.

Targeting Lymph Nodes with a Nanoparticle-Based Drug Delivery System

Targeting Lymph Nodes with a Nanoparticle-Based Drug Delivery System

Navigated ultrasound bronchoscopy with integrated positron emission tomography-A human feasibility study.

Patients suspected to have lung cancer, undergo endobronchial ultrasound bronchoscopy (EBUS) for the purpose of diagnosis and staging. For presumptive curable patients, the EBUS bronchoscopy is planned based on images and data from computed tomography (CT) images and positron emission tomography (PET). Our study aimed to evaluate the feasibility of a multimodal electromagnetic navigation platform for EBUS bronchoscopy, integrating ultrasound and segmented CT, and PET scan imaging data. The proof-of-concept study included patients with suspected lung cancer and pathological mediastinal/hilar lymph nodes identified on both CT and PET scans. Images obtained from these two modalities were segmented to delineate target lymph nodes and then incorporated into the CustusX navigation platform. The EBUS bronchoscope was equipped with a sensor, calibrated, and affixed to a 3D printed click-on device positioned at the bronchoscope's tip. Navigation accuracy was measured postoperatively using ultrasound recordings. The study enrolled three patients, all presenting with suspected mediastinal lymph node metastasis (N1-3). All PET-positive lymph nodes were displayed in the navigation platform during the EBUS procedures. In total, five distinct lymph nodes were sampled, yielding malignant cells from three nodes and lymphocytes from the remaining two. The median accuracy of the navigation system was 7.7 mm. Our study introduces a feasible multimodal electromagnetic navigation platform that combines intraoperative ultrasound with preoperative segmented CT and PET imaging data for EBUS lymph node staging examinations. This innovative approach holds promise for enhancing the accuracy and effectiveness of EBUS procedures.

Locoregional Ablative Radiation Therapy for Patients With Breast Cancer Unsuitable for Surgical Resection

Breast cancer patients unsuitable for surgical resection are typically managed with palliative systemic therapy alone. We report outcomes of 5-fraction ablative radiotherapy for non-resected breast cancers. Retrospective analysis of an institutional registry of breast cancer patients unsuitable for resection who underwent 35-40 Gy/5 fractions to the primary breast tumour and/or regional lymph nodes from 2014-2021. Primary outcomes were cumulative incidence of local failure (LF) and grade ≥3 toxicity (CTCAE v5.0). We reviewed 57 patients who received 61 treatment courses (median age of 81 years, range 38-99). Unresectable tumour (10%), patient refusal (18%), medical inoperability (35%), and metastatic disease (37%) were the causes of not having surgery. Five patients (8%) had previously undergone adjuvant locoregional radiotherapy. Fifty-four percent (n=33/61) of treatment courses targeted the breast only, 31% (n=19/61) both the breast and lymph nodes, and 15% (n=9/61) the lymph nodes only. Sixty-seven percent (n=35/52) of the courses that targeted the breast were delivered with partial breast irradiation and 33% (n=17/52) with whole breast radiotherapy (median dose of 25Gy in 5 fractions) ± simultaneous integrated boost to the primary tumour. Most primary tumours (65%, n=34/52) and target lymph nodes (61%, n=17/28) were treated with a dose of 35 Gy in 5 fractions. Most treatments (52%) were delivered with intensity-modulated radiotherapy (IMRT). Radiotherapy was delivered daily (20%), every other day (18%), twice weekly (36%) or weekly (26%). The 2-year cumulative incidence of LF was 11.4% and grade≥3 toxicity was 15.1%. The grade ≥3 toxicity was 6.5% for IMRT treatments, versus 7.7% for non-IMRT treatments targeting partial breast and/or lymph nodes (HR 1.13, P=0.92), versus 38.9% for non-IMRT treatments targeting the entire breast (HR 6.91, P=0.023). All grade ≥3 toxicity cases were radiation dermatitis. No cases of brachial plexopathy were observed. 35-40 Gy in 5 fractions is a safe and effective breast stereotactic body radiotherapy regimen and may be an attractive option for patients who are not surgical candidates. Highly conformal techniques (i.e. IMRT or partial breast irradiation) were associated with a reduced risk of toxicity and should be the preferred treatment approaches.

A European Society of Oncologic Imaging (ESOI) survey on the radiological assessment of response to oncologic treatments in clinical practice

ObjectivesTo present the results of a survey on the assessment of treatment response with imaging in oncologic patient, in routine clinical practice. The survey was promoted by the European Society of Oncologic Imaging to gather information for the development of reporting models and recommendations.MethodsThe survey was launched on the European Society of Oncologic Imaging website and was available for 3 weeks. It consisted of 5 sections, including 24 questions related to the following topics: demographic and professional information, methods for lesion measurement, how to deal with diminutive lesions, how to report baseline and follow-up examinations, which previous studies should be used for comparison, and role of RECIST 1.1 criteria in the daily clinical practice.ResultsA total of 286 responses were received. Most responders followed the RECIST 1.1 recommendations for the measurement of target lesions and lymph nodes and for the assessment of tumor response. To assess response, 48.6% used previous and/or best response study in addition to baseline, 25.2% included the evaluation of all main time points, and 35% used as the reference only the previous study. A considerable number of responders used RECIST 1.1 criteria in daily clinical practice (41.6%) or thought that they should be always applied (60.8%).ConclusionSince standardized criteria are mainly a prerogative of clinical trials, in daily routine, reporting strategies are left to radiologists and oncologists, which may issue local and diversified recommendations. The survey emphasizes the need for more generally applicable rules for response assessment in clinical practice.Critical relevance statementCompared to clinical trials which use specific criteria to evaluate response to oncological treatments, the free narrative report usually adopted in daily clinical practice may lack clarity and useful information, and therefore, more structured approaches are needed.Key points· Most radiologists consider standardized reporting strategies essential for an objective assessment of tumor response in clinical practice.· Radiologists increasingly rely on RECIST 1.1 in their daily clinical practice.· Treatment response evaluation should require a complete analysis of all imaging time points and not only of the last.Graphical

Assessment of the lung tissue fibrosis in workers exposed to silica-hazardous dust for a long time

Introduction. Silicosis is the most common and severe type of pneumoconiosis caused by inhalation of dust containing more than 10% of crystalline silica in the occupational setting. The chest X-ray plays a decisive role in the diagnosis of the disease.
 The purpose of our work was to establish lung tissue fibrosis in industrial workers suffering from silicosis.
 Materials and methods. In 2015–2022, ten patients with silicosis, employed at a Ural refractory manufacturing plant as press operators (Group 1) for the average of 17.23 ± 4.31 years, were examined at the Occupational Health Clinic of the Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers. The comparison group (Group 2) included 34 press operators without pneumoconiosis who had worked for more than 10 years in hazardous working conditions. The control group (Group 3) consisted of 32 people of different occupations unexposed to industrial dusts. All the subjects were matched by gender (male) and age (50.7 ± 5.25 years). Lung tissue fibrosis was measured by multislice computed tomography using a GE OPTIMA 660 128 Slice CT Scanner with accessories, GE HealthCare Japan, manufactured in 2012. The data were then analyzed in Statistica for Windows 7.
 Results. We established a decrease in tissue fibrosis in the apexes and inferior lobes of both lungs and an increase in the fibrosis in groups of target lymph nodes (11–14R, 2L, 10L) in the silicosis cases, and an increase in Hounsfield units in target groups of lymph nodes (2R, 4R, 10R, 11–14R, 2L, 11–14L) in the comparison group.
 Limitations. The study includes only workers engaged in refractory manufacturing with over 10 years of exposure to silica. For CT lung densitometry, the limitation is the permissible radiation dose of less than 5 mSv per year.
 Conclusion. The results of CT densitometry of the lungs and targeted groups of lymph nodes demonstrate its high efficiency in the quantitative assessment 
 of dust-related disorders in patients with silicosis and in experienced workers occupationally exposed to crystalline silica.

Nanovaccines for Advancing Long-Lasting Immunity against Infectious Diseases.

Infectious diseases, particularly life-threatening pathogens such as small pox and influenza, have substantial implications on public health and global economies. Vaccination is a key approach to combat existing and emerging pathogens. Immunological memory is an essential characteristic used to evaluate vaccine efficacy and durability and the basis for the long-term effects of vaccines in protecting against future infections; however, optimizing the potency, improving the quality, and enhancing the durability of immune responses remains challenging and a focus for research involving investigation of nanovaccine technologies. In this review, we describe how nanovaccines can address the challenges for conventional vaccines in stimulating adaptive immune memory responses to protect against reinfection. We discuss protein and nonprotein nanoparticles as useful antigen platforms, including those with highly ordered and repetitive antigen array presentation to enhance immunogenicity through cross-linking with multiple B cell receptors, and with a focus on antigen properties. In addition, we describe how nanoadjuvants can improve immune responses by providing enhanced access to lymph nodes, lymphnode targeting, germinal center retention, and long-lasting immune response generation. Nanotechnology has the advantage to facilitate vaccine induction of long-lasting immunity against infectious diseases, now and in the future.