Incomplete Intrapulmonary Lymph Node Retrieval After Routine Pathologic Examination of Resected Lung Cancer

2012 ◽  
Vol 30 (23) ◽  
pp. 2823-2828 ◽  
Author(s):  
Robert A. Ramirez ◽  
Christopher G. Wang ◽  
Laura E. Miller ◽  
Courtney A. Adair ◽  
Allen Berry ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Significant Proportion ◽  
External Control ◽  
Pathologic Examination ◽  
Resected Nsclc ◽  
Lymph Node Retrieval ◽  
Large Numbers ◽  
Pathologic Staging ◽  
Clinically Significant ◽  
Time Required

Purpose Pathologic nodal stage affects prognosis in patients with surgically resected non–small-cell lung cancer (NSCLC). Unlike examination of mediastinal lymph nodes (LNs), which depends on surgical practice, accurate examination of intrapulmonary (N1) nodes depends primarily on pathology practice. We investigated the completeness of N1 LN examination in NSCLC resection specimens and its potential impact on stage. Patients and Methods We performed a case-control study of a special pathologic examination (SPE) protocol using thin gross dissection with retrieval and microscopic examination of all LN-like material on remnant NSCLC resection specimens after routine pathologic examination (RPE). We compared LNs retrieved by the SPE protocol with nodes examined after RPE of the same lung specimens and with those of an external control cohort. Results We retrieved additional LNs in 66 (90%) of 73 patient cases and discovered metastasis in 56 (11%) of 514 retrieved LNs from 27% of all patients. We found unexpected LN metastasis in six (12%) of 50 node-negative patients. Three other patients had undetected satellite metastatic nodules. Pathologic stage was upgraded in eight (11%) of 73 patients. The time required for the SPE protocol decreased significantly with experience, with no change in the number of LNs found. Conclusion Standard pathology practice frequently leaves large numbers of N1 LNs unexamined, a clinically significant proportion of which harbor metastasis. By improving N1 LN examination, SPE can have an impact on prognosis and adjuvant management. We suggest adoption of the SPE to improve pathologic staging of resected NSCLC.

scholarly journals A phase II study of cisplatin plus vinorelbine combined with atezolizumab as adjuvant therapy for completely resected non-small-cell lung cancer with EGFR mutation (West Japan Oncology Group 11719L/ADJUST study)

2021 ◽  
Vol 13 ◽  
pp. 175883592098764
Author(s):  
Ryota Shibaki ◽  
Hiroaki Akamatsu ◽  
Terufumi Kato ◽  
Kazumi Nishino ◽  
Morihito Okada ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adjuvant Therapy ◽  
Egfr Mutation ◽  
Phase Ii Study ◽  
Small Cell ◽  
Small Cell Lung ◽  
Resected Nsclc ◽  
Egfr Mutated ◽  
Doublet Chemotherapy ◽  
Platinum Doublet

Background: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) is a standard treatment in EGFR-mutated advanced non-small-cell lung cancer (NSCLC); however, previous data have suggested that EGFR-TKI has limited potential as adjuvant therapy. On the contrary, based on subset analysis with the immune checkpoint inhibitor (ICI) plus platinum-doublet chemotherapy in advanced NSCLC with EGFR mutation, we hypothesized that this combination was worth testing as adjuvant therapy in patients with EGFR-mutated NSCLC. Methods: Herein, we introduce our phase II study of cisplatin plus vinorelbine combined with atezolizumab as adjuvant therapy for completely resected NSCLC with EGFR mutation. Accrued patients will be pathological stage II–IIIA with completely resected NSCLC and whose tumors have EGFR mutation. Treatment comprises four cycles of cisplatin plus vinorelbine combined with atezolizumab followed by maintenance with atezolizumab. The primary endpoint is the disease-free survival (DFS) rate at 2 years. Secondary endpoints are DFS, overall survival, and safety. In total, 18 patients will be enrolled in this study. Discussion: Ongoing phase III trials of adjuvant ICI allow the inclusion of patients with EGFR mutation, but our current trial will provide the earliest clinical data on the efficacy of platinum-doublet chemotherapy with atezolizumab.

scholarly journals Health-related quality of life and anxiety in the PAN-CAN lung cancer screening cohort

BMJ Open ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. e024719 ◽  
Author(s):  
Niloofar Taghizadeh ◽  
Alain Tremblay ◽  
Sonya Cressman ◽  
Stuart Peacock ◽  
Annette M McWilliams ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Screening ◽  
Lung Cancer Screening ◽  
Health Related Quality ◽  
Related Quality ◽  
Health Related ◽  
Anxiety Levels ◽  
Clinically Significant ◽  
Baseline Screening

ObjectivesThe impact of lung cancer screening with low-dose chest CT (LDCT) on participants’ anxiety levels and health-related quality of life (HRQoL) is an important consideration in the implementation of such programmes. We aimed to describe changes in anxiety and HRQoL in a high-risk Canadian cohort undergoing LDCT lung cancer screening.Methods2537 subjects who had 2% or greater lung cancer risk over 6 years using a risk prediction tool were recruited from eight centres across Canada in the Pan-Canadian Early Detection of Lung Cancer Study (2008–2010). We compared HRQoL and anxiety levels before and after screening of 1237 participants with LDCT (excluding a subset of 1300 participants who also underwent autofluorescence bronchoscopy screening), as well as after investigations performed because of a positive screening examination. The 12-item short-form Physical and Mental Component Scales (SF-12), EQ-5D-3L scores and State Trait Anxiety Inventory-State anxiety were used at each assessment.ResultsOverall, there were no clinically significant differences in HRQoL outcomes between baseline and each of the survey time points following initial screening. No mean change in anxiety in the overall cohort was noted following baseline LDCT, but more participants had clinically significant increase in anxiety versus decrease after baseline screening (increase >minimal clinically important difference (MCID) (n=180) vs decrease >MCID (n=50), p<0.001). This finding persisted but to a lesser degree at the 12 month time point (increase >MCID (n=146) vs decrease >MCID (n=87), p<0.001).ConclusionsCT screening for lung cancer has no major overall impact on HRQoL among participants, although a minority of participants (number-needed-to-harm=7 after baseline screening and 18 at 1 year) demonstrated clinically significant increased anxiety levels.Trialregistration numberNCT00751660; Results.

Usefulness of CT Chest in Determining Clinically Significant Mediastinal Lymphadenopathy in Patients With Non-Small Cell Lung Cancer (NSCLC)

CHEST Journal ◽  
2003 ◽  
Vol 124 (4) ◽  
pp. 194S
Author(s):  
Mazen Alakhras ◽  
Geetha Kanajam ◽  
Damodhar Nerella ◽  
Karthikeyan Kanagarajan ◽  
Depakkumar Malli ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Mediastinal Lymphadenopathy ◽  
Small Cell Lung ◽  
Clinically Significant

scholarly journals ELIGIBILITY FOR LOW-DOSE COMPUTED TOMOGRAPHY LUNG CANCER SCREENING IN OLDER ASIAN AMERICAN SMOKERS

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S189-S189
Author(s):  
Chien-Ching Li ◽  
Kelsey Choi ◽  
Alicia Matthews ◽  
Raj Shah
Keyword(s):  
Computed Tomography ◽  
Lung Cancer ◽  
Asian American ◽  
Low Dose ◽  
Task Force ◽  
Significant Proportion ◽  
Lung Cancer Screening ◽  
Lung Cancer Mortality ◽  
Eligibility Criteria ◽  
Low Dose Computed Tomography

Abstract Lung cancer is the leading cause of cancer-related deaths in Asian Americans. Low-dose computed tomography lung cancer (LDCT) screening is an effective way to decrease lung cancer mortality. This study aimed to examine the difference in LDCT screening eligibility among Asian American subgroups. The National Health Interview Survey data (2006-2016) was analyzed. The U.S. Preventive Services Task Force guideline was used to determine the LDCT eligibility. A higher and statistically significant proportion of current Filipino smokers (35.4%) met LDCT screening eligibility criteria compared to Chinese (26.5%) and other Asian smokers (22.7%) (p=0.02). Hierarchical logistic regression results further showed that Filipino were more likely to meet LDCT screening criteria than other Asian while adjusting demographics (OR=1.87; p=0.01). The differences in LDCT screening eligibility no longer existed after additionally adjusting socioeconomic factors as well as perceived health status. Future targeted outreach and intervention research is needed for Filipinos with lower socioeconomic status.

scholarly journals Conserved noncoding elements influence the transposable element landscape in Drosophila

2018 ◽  
Author(s):  
Manee M. Manee ◽  
John Jackson ◽  
Casey M. Bergman
Keyword(s):  
Transposable Element ◽  
Significant Proportion ◽  
Purifying Selection ◽  
Noncoding Dna ◽  
Frequency Spectra ◽  
Noncoding Regions ◽  
Selective Constraints ◽  
Large Numbers ◽  
Random Expectation ◽  
Conserved Noncoding Elements

AbstractHighly conserved noncoding elements (CNEs) comprise a significant proportion of the genomes of multicellular eukaryotes. The function of most CNEs remains elusive, but growing evidence indicates they are under some form of purifying selection. Noncoding regions in many species also harbor large numbers of transposable element (TE) insertions, which are typically lineage specific and depleted in exons because of their deleterious effects on gene function or expression. However, it is currently unknown whether the landscape of TE insertions in noncoding regions is random or influenced by purifying selection on CNEs. Here we combine comparative and population genomic data in Drosophila melanogaster to show that abundance of TE insertions in intronic and intergenic CNEs is reduced relative to random expectation, supporting the idea that selective constraints on CNEs eliminate a proportion of TE insertions in noncoding regions. However, we find no difference in the allele frequency spectra for polymorphic TE insertions in CNEs versus those in unconstrained spacer regions, suggesting that the distribution of fitness effects acting on observable TE insertions is similar across different functional compartments in noncoding DNA. Our results provide evidence that selective constraints on CNEs contribute to shaping the landscape of TE insertion in eukaryotic genomes, and provide further evidence supporting the conclusion that CNEs are indeed functionally constrained and not simply mutational cold spots.

scholarly journals Tumour islet Foxp3+ T-cell infiltration predicts poor outcome in nonsmall cell lung cancer

2015 ◽  
Vol 46 (6) ◽  
pp. 1762-1772 ◽  
Author(s):  
Dermot S. O'Callaghan ◽  
Elton Rexhepaj ◽  
Kathy Gately ◽  
Linda Coate ◽  
David Delaney ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
T Lymphocytes ◽  
Cell Lung Cancer ◽  
Positive Association ◽  
Nonsmall Cell Lung Cancer ◽  
T Cell Infiltration ◽  
Resected Nsclc ◽  
Lymphoid Infiltration ◽  
The Impact

The impact of host immunity on outcome in nonsmall cell lung cancer (NSCLC) is controversial. We examined the relationship between lymphoid infiltration patterns in NSCLC and prognosis.Tumour- and stroma-infiltrating CD3+, CD8+ and forkhead box P3 (Foxp3)+ T-lymphocytes were identified using immunohistochemistry and a novel image analysis algorithm to assess total, cytotoxic and regulatory T-lymphocyte counts, respectively, in 196 NSCLC cases. The median cell count was selected as a cut-point to define patient subgroups and the ratio of the corresponding tumour islet:stroma (TI/S) counts was determined.There was a positive association between overall survival and increased CD8+ TI/S ratio (hazard ratio (HR) for death 0.44, p<0.001) but an inverse relationship between Foxp3+ TI/S ratio and overall survival (HR 4.86, p<0.001). Patients with high CD8+ islet (HR 0.48, p<0.001) and Foxp3+ stromal (HR 0.23, p<0.001) counts had better survival, whereas high CD3+ and CD8+ stromal counts and high Foxp3+ islet infiltration conferred a worse survival (HR 1.55, 2.19 and 3.14, respectively). By multivariate analysis, a high CD8+ TI/S ratio conferred an improved survival (HR 0.48, p=0.002) but a high Foxp3+ TI/S ratio was associated with worse survival (HR 3.91, p<0.001).Microlocalisation of infiltrating T-lymphocytes is a powerful predictor of outcome in resected NSCLC.

scholarly journals Positive tumour CD47 expression is an independent prognostic factor for recurrence in resected non-small cell lung cancer

ESMO Open ◽  
2020 ◽  
Vol 5 (4) ◽  
pp. e000823
Author(s):  
Yan Xu ◽  
Ji Li ◽  
Bing Tong ◽  
Minjiang Chen ◽  
Xiaoyan Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Prognostic Factor ◽  
Infectious Diseases ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Independent Prognostic Factor ◽  
Small Cell Lung ◽  
Cox Regression Analysis ◽  
Resected Nsclc

BackgroundImmunotherapy is a promising advance in oncology. Limited information exists regarding the interrelationship between CD47 expression and tumour-associated macrophage-related immuno-microenvironment in patients with non-small cell lung cancer (NSCLC). These factors may predict novel immunotherapy efficacy.Patients and methodsCD47 and PD-L1 expression was retrospectively assessed in 191 resected NSCLC specimens via immunohistochemistry. Forty-six patients with pulmonary infectious diseases were enrolled as the control group. The infiltration of macrophages (M2 and M1) and CD8+ T-lymphocytes was evaluated via dual-immunofluorescence staining. Targeted DNA sequencing was performed on NSCLC specimens. Survival analysis was performed using the Cox model.ResultsUsing 2+/3+ as a CD47 positive (CD47pos) expression cut-off, the prevalence of CD47pos expression in NSCLC was 33.0% (63/191), significantly higher than in pulmonary infectious diseases. CD47pos expression was significantly higher in female, non-smoking and adenocarcinoma patients (p=0.020, p<0.001 and p<0.001, respectively). Furthermore, CD47pos expression was significantly correlated with epidermal growth factor receptor mutation (p<0.001). The expression of CD47 (H-score) in NSCLC was negatively correlated with tumour PD-L1 expression (p=0.0346) and tumour mutation burden (p=0.0107). CD47pos expression was independently correlated with poor disease-free survival in patients with resected NSCLC in multivariate Cox regression analysis (p=0.035).ConclusionThis study revealed the demographic, molecular and immuno-microenvironment characteristics of CD47 expression in NSCLC. We identified tumour CD47pos expression as an independent prognostic factor for recurrence in resected NSCLC. Our findings illustrate the potential of anti-CD47 treatment in NSCLC.

scholarly journals Tumor Mutation Burden as a Biomarker in Resected Non–Small-Cell Lung Cancer

2018 ◽  
Vol 36 (30) ◽  
pp. 2995-3006 ◽  
Author(s):  
Siddhartha Devarakonda ◽  
Federico Rotolo ◽  
Ming-Sound Tsao ◽  
Irena Lanc ◽  
Elisabeth Brambilla ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adjuvant Chemotherapy ◽  
Disease Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Tumor Mutation Burden ◽  
Resected Nsclc ◽  
Mutation Burden ◽  
Disease Free

Purpose The survival benefit with adjuvant chemotherapy for patients with resected stage II-III non–small-cell lung cancer (NSCLC) is modest. Efforts to develop prognostic or predictive biomarkers in these patients have not yielded clinically useful tests. We report findings from the Lung Adjuvant Cisplatin Evaluation (LACE)-Bio-II study, in which we analyzed next-generation sequencing and long-term outcomes data from > 900 patients with early-stage NSCLC treated prospectively in adjuvant landmark clinical trials. We used a targeted gene panel to assess the prognostic and predictive effect of mutations in individual genes, DNA repair pathways, and tumor mutation burden (TMB). Methods A total of 908 unmatched, formalin-fixed, paraffin-embedded, resected lung cancer tumor specimens were sequenced using a targeted panel of 1,538 genes. Stringent filtering criteria were applied to exclude germline variants and artifacts related to formalin fixation. Disease-free survival, overall survival, and lung cancer—specific survival (LCSS) were assessed in Cox models stratified by trial and adjusted for treatment, age, sex, performance score, histology, type of surgery, and stage. Results Nonsynonymous mutations were identified in 1,515 genes in 908 tumor samples. High nonsynonymous TMB (> 8 mutations/Mb) was prognostic for favorable outcomes (ie, overall survival, disease-free survival, and LCSS) in patients with resected NSCLC. LCSS benefit with adjuvant chemotherapy was more pronounced in patients with low nonsynonymous TMBs (≤ 4 mutations/Mb). Presence of mutations in DNA repair pathways, tumor-infiltrating lymphocytes, TP53 alteration subtype, and intratumor heterogeneity was neither prognostic nor predictive. Statistically significant effect of mutations in individual genes was difficult to determine due to high false-discovery rates. Conclusion High nonsynonymous TMB was associated with a better prognosis in patients with resected NSCLC. In addition, the benefit of adjuvant chemotherapy on LCSS was more pronounced in patients with low nonsynonymous TMBs. Studies are warranted to confirm these findings.

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