scholarly journals Tumour draining lymph node-generated CD8 T cells play a role in controlling lung metastases after a primary tumour is removed but not when adjuvant immunotherapy is used

2021 ◽  
Author(s):  
Fear VS ◽  
Forbes CA ◽  
Neeve SA ◽  
Fisher SA ◽  
Chee J ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Metastatic Disease ◽  
Clinical Setting ◽  
Primary Tumour ◽  
Adjuvant Immunotherapy ◽  
Time Of Surgery ◽  
Lymph Node Resection ◽  
Metastatic Lung

AbstractSurgical resection of cancer remains the frontline therapy for millions of patients annually, but post-operative recurrence is common, with a relapse rate of around 45% for non-small cell lung cancer. The tumour draining lymph nodes (dLN) are resected at the time of surgery for staging purposes, and this cannot be a null event for patient survival and future response to immune checkpoint blockade treatment. This project investigates cancer surgery, lymphadenectomy, onset of metastatic disease, and response to immunotherapy in a novel model that closely reflects the clinical setting. In a murine metastatic lung cancer model, primary subcutaneous tumours were resected with associated dLNs remaining intact, completely resected or partially resected. Median survival after surgery was significantly shorter with complete dLN resection at the time of surgery (49 days (95%CI)) compared to when lymph nodes remained intact (> 88 days; p < 0.05). Survival was partially restored with incomplete lymph node resection and CD8 T cell dependent. Treatment with aCTLA4 whilst effective against the primary tumour was ineffective for metastatic lung disease. Conversely, aPD-1/aCD40 treatment was effective in both the primary and metastatic disease settings and restored the detrimental effects of complete dLN resection on survival. In this pre-clinical lung metastatic disease model that closely reflects the clinical setting, we observe decreased frequency of survival after complete lymphadenectomy, which was ameliorated with partial lymph node removal or with early administration of aPD-1/aCD40 therapy. These findings have direct relevance to surgical lymph node resection and adjuvant immunotherapy in lung cancer, and perhaps other cancer, patients.

scholarly journals Quantitative mass spectrometry to interrogate proteomic heterogeneity in metastatic lung adenocarcinoma and validate a novel somatic mutation CDK12-G879V

2018 ◽  
Author(s):  
Xu Zhang ◽  
Khoa Dang Nguyen ◽  
Paul Rudnick ◽  
Nitin Roper ◽  
Emily Kawaler ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Lung Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Lung Adenocarcinoma ◽  
Mass Spectrometry Data ◽  
Patient Specific ◽  
Metastatic Site ◽  
Metastatic Lung ◽  
Metastatic Sites

AbstractLung cancer is the leading cause of cancer death both in men and women. Tumor heterogeneity is an impediment to targeted treatment of all cancers, including lung cancer. Here, we sought to characterize changes in tumor proteome and phosphoproteome by longitudinal, prospective collection of tumor tissue of an exceptional responder lung adenocarcinoma patient who survived with metastatic lung adenocarcinoma for more than seven years with HER2-directed therapy in combination with chemotherapy. We employed “Super-SILAC” and TMT labeling strategies to quantify the proteome and phosphoproteome of a lung metastatic site and ten different metastatic progressive lymph nodes collected across a span of seven years, including five lymph nodes procured at autopsy. We identified specific signaling networks enriched in lung compared to the lymph node metastatic sites. We correlated the changes in protein abundance with changes in copy number alteration (CNA) and transcript expression. To further interrogate the mass spectrometry data, patient-specific database was built incorporating all the somatic variants identified by whole genome sequencing (WGS) of genomic DNA from the lung, one lymph node metastatic site and blood. An extensive validation pipeline was built for confirmation of variant peptides. We validated 360 spectra corresponding to 55 germline and 6 somatic variant peptides. Targeted MRM assays demonstrated expression of two novel variant somatic peptides, CDK12-G879V and FASN-R1439Q, with expression in lung and lymph node metastatic sites, respectively. CDK12 G879V mutation likely results in a nonfunctional CDK12 kinase and chemotherapy susceptibility in lung metastatic sites. Knockdown of CDK12 in lung adenocarcinoma cells results in increased chemotherapy sensitivity, explaining the complete resolution of the lung metastatic sites in this patient.

Size distribution and metastasis in discarded intrapulmonary lymph nodes (LN) after lung cancer resection.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7072-7072
Author(s):  
Laura Elizabeth Miller ◽  
Robert A. Ramirez ◽  
Christopher Gene Wang ◽  
Courtney A Adair ◽  
Allen Berry ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Metastatic Disease ◽  
Lung Resection ◽  
Optimal Number ◽  
Pathology Report ◽  
Test Results ◽  
Cancer Resection ◽  
T Category

7072^ Background: Lymph node (LN) status is the most important prognostic determinant after resection of lung cancer. 18% of a SEER cohort and 12% of a Memphis cohort had no LNs examined (pNx). Patients with pNx have inferior survival to T-category matched pN0 patients with at least 1 LN examined. The optimal number of LN needed to safely declare a patient pN0 may be >10. Less than 20% of resections in SEER achieve this. We hypothesized that a significant number of intrapulmonary LNs are left unexamined and some may harbor metastatic disease. We report the size characteristics of materials examined in a re-dissection protocol to test this hypothesis. Methods: Prospective study of lung resection specimens re-dissected after signout of the final pathology report. Remnant lung material was dissected with thin cuts and all LN-like material was retrieved for microscopic examination, irrespective of size or location. The size of non-LN tissue, LN without metastasis and LN with metastases were compared using the Wilcoxon-Mann-Whitney test. Results: 112 specimens were examined and 1,094 LN-like materials were retrieved. 749 (69%) proved to be LN tissue. 71 (10%) LNs retrieved had metastasis. Non-LN tissue was significantly smaller than LN tissue (p<0.0001). LNs with metastasis were significantly larger than those without metastasis (p <0.0001). 60% of materials >2cm were LNs with metastasis. 7% of materials <1cm were LN with metastasis. 52% of LNs with metastasis, and 55% of LNs without metastasis measured from 0.5 to 1.5cm (Table). Majority of LNs >2cm had metastatic disease, but 40% did not; a notable proportion of LNs with metastasis were small. Nearly equal percentages of LNs with and without metastasis were found in the range of 0.5-1.5cm. Conclusions: Statistical differences in size between lymph nodes with and without metastasis is clinically meaningless due to broad overlap. LN size alone is not an adequate predictor of LN metastasis. [Table: see text]

The number of lymph nodes with metastatic disease portends for a poorer prognosis in women with stage IIIC-IV endometrioid uterine cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5039-5039
Author(s):  
J. K. Chan ◽  
M. K. Cheung ◽  
K. Osann ◽  
A. Husain ◽  
N. N. Teng ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Metastatic Disease ◽  
Uterine Cancer ◽  
Adjuvant Radiation ◽  
Nodal Metastases ◽  
Stage Iiic ◽  
Node Positive ◽  
Lymph Node Resection

5039 Background: To determine the prognosis of women with IIIC-IV endometrioid uterine cancer based on the number lymph nodes with metastatic disease Methods: Demographic and clinico-pathologic information were obtained from the Surveillance, Epidemiology and End Results Program from 1988–2001 and analyzed using Kaplan-Meier methods and Cox proportional hazards regression. Results: Of the 1,222 women diagnosed with stage IIIC-IV endometrioid uterine cancer with nodal disease, the median age was 64 (range: 28–93). All patients underwent surgical staging including a lymph node assessment and were found to have nodal metastases. 639 (52.3%) had stage IIIC, 24 (2.0%) IVA, and 559 (45.7%) IVB disease. The study cohort was divided in three subgroups based on the number of positive nodal metastases: 1, 2–5, and >5. The 5-year overall disease-specific survivals of women with 1, 2–5, and >5 positive nodes were 68.1%, 55.1% and 46.4%, respectively (p < 0.0001). The increasing number of positive nodes was associated with a worsening survival in stage IIIC (77.1%, 60.9%, 69.1%; p = 0.003) and stage IV (50.9%, 49.8%, 38.9%; p = 0.09) diseases. It appears that the extent of benign nodal resection attenuates the increase in the mortality associated with a higher number of positive nodes (see table ). Women with higher number of positive nodes received significantly less adjuvant radiotherapy at 76.8%, 59.5%, and 56.7% respectively. On multivariate analysis, age, stage, grade, number of positive lymph nodes and extent of lymph node resection were significant independent prognostic factors for survival. However, adjuvant radiation was not an important independent prognostic factor in multivariate analysis. Conclusion: Women with node positive endometrioid uterine cancers have a decreased survival associated with increasing number of positive nodes. Our data suggests that the extent of lymph node resection improves the survival of patients with node-positive uterine cancer. [Table: see text] No significant financial relationships to disclose.

scholarly journals Endobronchial ultrasound-guided transbronchial needle aspiration for lung cancer staging: early experience in Brazil,

2015 ◽  
Vol 41 (1) ◽  
pp. 23-30 ◽  
Author(s):  
Viviane Rossi Figueiredo ◽  
Paulo Francisco Guerreiro Cardoso ◽  
Márcia Jacomelli ◽  
Sérgio Eduardo Demarzo ◽  
Addy Lidvina Mejia Palomino ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Cancer Staging ◽  
Accurate Method ◽  
Needle Aspiration ◽  
Endobronchial Ultrasound ◽  
Lymph Node Staging ◽  
Ultrasound Guided ◽  
Transbronchial Needle Aspiration

Objective: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive, safe and accurate method for collecting samples from mediastinal and hilar lymph nodes. This study focused on the initial results obtained with EBUS-TBNA for lung cancer and lymph node staging at three teaching hospitals in Brazil. Methods: This was a retrospective analysis of patients diagnosed with lung cancer and submitted to EBUS-TBNA for mediastinal lymph node staging. The EBUS-TBNA procedures, which involved the use of an EBUS scope, an ultrasound processor, and a compatible, disposable 22 G needle, were performed while the patients were under general anesthesia. Results: Between January of 2011 and January of 2014, 149 patients underwent EBUS-TBNA for lymph node staging. The mean age was 66 ± 12 years, and 58% were male. A total of 407 lymph nodes were sampled by EBUS-TBNA. The most common types of lung neoplasm were adenocarcinoma (in 67%) and squamous cell carcinoma (in 24%). For lung cancer staging, EBUS-TBNA was found to have a sensitivity of 96%, a specificity of 100%, and a negative predictive value of 85%. Conclusions: We found EBUS-TBNA to be a safe and accurate method for lymph node staging in lung cancer patients.

scholarly journals From Raw Pixels to Recurrence Image for Deep Learning of Benign and Malignant Mediastinal Lymph Nodes on Computed Tomography

2020 ◽  
Author(s):  
Tuan Pham
Keyword(s):  
Computed Tomography ◽  
Lung Cancer ◽  
Deep Learning ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Mediastinal Lymph Node ◽  
Survival Rates ◽  
Primary Lung Cancer ◽  
Lymph Node Status ◽  
Mediastinal Lymph Nodes

<div>Lung cancer causes the most cancer deaths worldwide and has one of the lowest five-year survival rates of all cancer types. It is reported that more than half of patients with lung cancer die within one year of being diagnosed. Because mediastinal lymph node status is the most important factor for the treatment and prognosis of lung cancer, the aim of this study is to improve the predictive value in assessing the computed tomography (CT) of mediastinal lymph-node malignancy in patients with primary lung cancer. This paper introduces a new method for creating pseudo-labeled images of CT regions of mediastinal lymph nodes by using the concept of recurrence analysis in nonlinear dynamics for the transfer learning. Pseudo-labeled images of original CT images are used as input into deep-learning models. Three popular pretrained convolutional neural networks (AlexNet, SqueezeNet, and DenseNet-201) were used for the implementation of the proposed concept for the classification of benign and malignant mediastinal lymph nodes using a public CT database. In comparison with the use of the original CT data, the results show the high performance of the transformed images for the task of classification. The proposed method has the potential for differentiating benign from malignant mediastinal lymph nodes on CT, and may provide a new way for studying lung cancer using radiology imaging. </div><div><br></div>

Metastatic Lung Cancer Without Regional Lymph Node Swelling

CHEST Journal ◽  
2001 ◽  
Vol 120 (2) ◽  
pp. 689-690 ◽  
Author(s):  
Hiroaki Satoh ◽  
Hiroichi Ishikawa ◽  
Yuko T. Yamashita ◽  
Morio Ohtsuka ◽  
Kiyohisa Sekizawa
Keyword(s):  
Lung Cancer ◽  
Lymph Node ◽  
Regional Lymph Node ◽  
Metastatic Lung Cancer ◽  
Metastatic Lung ◽  
Lymph Node Swelling

676 NECESSITY OF EXTENDED LOWER PARATRACHEAL LYMPH NODE RESECTION DURING ESOPHAGECTOMY FOR CANCER

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
C Mann ◽  
F Berlth ◽  
E Hadzijusufovic ◽  
E Uzun ◽  
E Tagkalos ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Esophageal Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Cell Carcinoma ◽  
P Value ◽  
Lymph Node Resection ◽  
Paratracheal Lymph Node ◽  
Esophagectomy For Cancer

Abstract Objective To evaluate the impact of lower paratracheal lymph node resection on oncological radicality and complication rate during esophagectomy for cancer. Backround The ideal extend of lymphadenectomy (LAD) in esophageal surgery is debated. Until today, there has been no proof for improved survival after standardized paratracheal lymph node resection performing oncological esophagectomy. Methods Lymph nodes from the lower paratracheal station are not standardly resected during 2-field Ivor-Lewis esophagectomy for esophageal cancer. Retrospectively, we identified 200 patients operated in our center for esophageal cancer from January 2017—December 2019. Histopathologically, 143 patients suffered from adenocarcinoma, 53 patients from squamous cell carcinoma, two patients from neuroendocrine carcinoma, and one from melanoma of the esophagus. Patients with and without lower paratracheal LAD were compared to patients regarding demographic data, tumor characteristics, operative details, postoperative complications, tumor recurrence and overall survival. Results 103 of 200 patients received lower paratracheal lymph node resection. On average, six lymph nodes were resected in the paratracheal region with histopathological cancer positivity in two patients. Those two patients suffered from neuroendocrine carcinoma and melanoma, none of the AC or SCC patients were positive. There was no significant difference between both groups regarding age, gender, BMI, or comorbidity. Harvesting of lower paratracheal lymph nodes was associated with less postoperative overall complications (p-value 0,029). Regarding overall survival and recurrence rate no difference could be detected between both groups (p-value 0,168, respectively 0,371). Conclusion The resection of lower paratracheal lymph nodes during esophagectomy seems not mandatory for distal squamous cell carcinoma or adenocarcinoma of the esophagus. It may be necessary in NEC, Melanoma of the esophagus or on demand if suspicious LN are detected in the CT scan. No increase of morbidity was caused by paratracheal dissection.

scholarly journals Number of Lymph Nodes and Metastatic Lymph Node Ratio Are Associated With Survival in Lung Cancer

2012 ◽  
Vol 93 (5) ◽  
pp. 1614-1620 ◽  
Author(s):  
Chukwumere E. Nwogu ◽  
Adrienne Groman ◽  
Daniel Fahey ◽  
Sai Yendamuri ◽  
Elisabeth Dexter ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Lymph Node Ratio ◽  
Metastatic Lymph Node ◽  
Metastatic Lymph ◽  
Node Ratio
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