scholarly journals Targeted screening for lung cancer with autoantibodies.

2021 ◽  
Author(s):  
Frank Sullivan ◽  
Frances Mair ◽  
Will Anderson ◽  
Pauline Armory ◽  
Andrew Briggs ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Resource Constraints ◽  
Early Stage ◽  
False Positive Rate ◽  
Lung Cancer Mortality ◽  
Treatment Modalities ◽  
Early Stage Disease ◽  
Targeted Screening ◽  
Resource Requirements ◽  
Positive Rate

Earlier detection of lung cancer is possible, but difficult and costly to achieve. Screening with Low Dose Computed Tomography (LDCT)scanning has been shown to reduce mortality by 20-25% over the past decade but uptake amongst those most likely to suffer the disease has been slow. Resource constraints and a high false positive rate have also limited adoption of LDCT in many health systems. Targeted screening of people most likely to benefit using a range of biomarkers may be one way to improve the yield and reduce the resource requirements of LDCT. Autoantibodies, which amplify the signal produced by cancer derived proteins, are present in the blood of people mounting an immune response to cancer are a potential way to select those at highest risk. We have followed up 12 208 people enrolled in the ECLS trial for three years and shown that the specificity for early stage (I &II) disease is 90.3% throughout that period. More cancers were detected in the control than the intervention arm of the trial (101V 83). Sensitivity was 77.8% after 6 months and dropped to 46.4% after 3 years. At the end of three years the hazard ratios (95%CI) for All Cause, Cancer Specific and Lung Cancer Mortality was 0.82(0.67-1.01), 0.72(0.54-0.97) and 0.70(0.46-1.08) respectively for those randomised to Early CDT testing. As a range of treatment modalities become increasingly more effective it is even more important to target LDCT on those most likely to have early stage disease. Autoantibody testing may be one method of targeting early detection on those most likely to benefit.

Worldwide Overview of the Current Status of Lung Cancer Diagnosis and Treatment

2012 ◽  
Vol 136 (12) ◽  
pp. 1478-1481 ◽  
Author(s):  
Paul A. Bunn
Keyword(s):  
Lung Cancer ◽  
Cancer Mortality ◽  
Kinase Inhibitors ◽  
False Positive Rate ◽  
Lung Cancer Mortality ◽  
Current Status ◽  
Advanced Lung Cancer ◽  
Lung Cancer Diagnosis ◽  
Positive Rate ◽  
Inhaled Prostacyclin

Lung cancer is the leading worldwide cause of cancer deaths. Smoking is the dominant cause of lung cancer and smoking cessation is the established method to reduce lung cancer mortality. While lung cancer risk is reduced in former smokers, they have a lifelong increase in risk, compared to never-smokers. Novel chemoprevention strategies, such as oral or inhaled prostacyclin analogs, hold promise for these subjects. Low-dose spiral computed tomography screening reduced lung cancer mortality by 20% in high-risk heavy smokers older than 50 years. However, the high false-positive rate (96%) means that screened patients required controlled follow-up in experienced centers. An increasing percentage of patients with advanced lung cancer have molecular drivers in genes for which oral tyrosine kinase inhibitors have been developed.

scholarly journals Implementation of targeted screening for lung cancer in a high-risk population within routine NHS practice using low-dose computed tomography

Thorax ◽  
2020 ◽  
Vol 75 (4) ◽  
pp. 348-350 ◽  
Author(s):  
Helen Grover ◽  
Thomas Ross ◽  
Elizabeth Fuller
Keyword(s):  
Lung Cancer ◽  
Low Dose ◽  
Screening Programme ◽  
Early Stage ◽  
High Risk Population ◽  
Curative Intent ◽  
Early Stage Disease ◽  
Stage Disease ◽  
Targeted Screening ◽  
Low Dose Computed Tomography

We report a primary care-based lung cancer targeted screening programme using low-dose CT (LDCT) in South Tyneside and Sunderland. Ever smokers with ≥10 pack-years aged 55–74 years were identified at annual COPD review. 925 individuals attended for LDCT. 2% (n=19/925) had lung cancer diagnosed. 66.7% (n=14/21) had early stage disease and 78.9% (n=15/19) were offered treatment with curative intent. 79.3% of individuals attending for LDCT were ranked in the lowest deprivation quintiles. This approach has been successfully established in routine NHS practice; it is effective with improvements in stage of disease and engages individuals in deprived areas.

scholarly journals Surgery in Small-Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 390
Author(s):  
Nicola Martucci ◽  
Alessandro Morabito ◽  
Antonello La Rocca ◽  
Giuseppe De Luca ◽  
Rossella De Cecio ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Small Cell ◽  
Stage I ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Early Stage Disease ◽  
Stage Disease

Small-cell lung cancer (SCLC) is one of the most aggressive tumors, with a rapid growth and early metastases. Approximately 5% of SCLC patients present with early-stage disease (T1,2 N0M0): these patients have a better prognosis, with a 5-year survival up to 50%. Two randomized phase III studies conducted in the 1960s and the 1980s reported negative results with surgery in SCLC patients with early-stage disease and, thereafter, surgery has been largely discouraged. Instead, several subsequent prospective studies have demonstrated the feasibility of a multimodality approach including surgery before or after chemotherapy and followed in most studies by thoracic radiotherapy, with a 5-year survival probability of 36–63% for patients with completely resected stage I SCLC. These results were substantially confirmed by retrospective studies and by large, population-based studies, conducted in the last 40 years, showing the benefit of surgery, particularly lobectomy, in selected patients with early-stage SCLC. On these bases, the International Guidelines recommend a surgical approach in selected stage I SCLC patients, after adequate staging: in these cases, lobectomy with mediastinal lymphadenectomy is considered the standard approach. In all cases, surgery can be offered only as part of a multimodal treatment, which includes chemotherapy with or without radiotherapy and after a proper multidisciplinary evaluation.

scholarly journals A population-based analysis of spirometry use and the prevalence of chronic obstructive pulmonary disease in lung cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sophie Corriveau ◽  
Gregory R. Pond ◽  
Grace H. Tang ◽  
John R. Goffin
Keyword(s):  
Lung Cancer ◽  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Early Stage ◽  
Advanced Lung Cancer ◽  
Public Healthcare ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Early Stage Disease ◽  
Morbidity Score

Abstract Background Chronic obstructive pulmonary disease (COPD) and lung cancer are associated diseases. COPD is underdiagnosed and thus undertreated, but there is limited data on COPD diagnosis in the setting of lung cancer. We assessed the diagnosis of COPD with lung cancer in a large public healthcare system. Methods Anonymous administrative data was acquired from ICES, which links demographics, hospital records, physician billing, and cancer registry data in Ontario, Canada. Individuals age 35 or older with COPD were identified through a validated, ICES-derived cohort and spirometry use was derived from physician billings. Statistical comparisons were made using Wilcoxon rank sum, Cochran-Armitage, and chi-square tests. Results From 2002 to 2014, 756,786 individuals were diagnosed with COPD, with a 2014 prevalence of 9.3%. Of these, 51.9% never underwent spirometry. During the same period, 105,304 individuals were diagnosed with lung cancer, among whom COPD was previously diagnosed in 34.9%. Having COPD prior to lung cancer was associated with lower income, a rural dwelling, a lower Charlson morbidity score, and less frequent stage IV disease (48 vs 54%, p < 0.001). Spirometry was more commonly undertaken in early stage disease (90.6% in stage I-II vs. 54.4% in stage III-IV). Conclusion Over a third of individuals with lung cancer had a prior diagnosis of COPD. Among individuals with advanced lung cancer, greater use of spirometry and diagnosis of COPD may help to mitigate respiratory symptoms.

scholarly journals Radiomics is feasible for prediction of spread through air spaces in patients with nonsmall cell lung cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuki Onozato ◽  
Takahiro Nakajima ◽  
Hajime Yokota ◽  
Jyunichi Morimoto ◽  
Akira Nishiyama ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Predictive Model ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Characteristic Curve ◽  
Sublobar Resection ◽  
Tumor Spread ◽  
Early Stage Disease ◽  
Significant Difference ◽  
Spread Through Air Spaces

AbstractTumor spread through air spaces (STAS) in non-small-cell lung cancer (NSCLC) is known to influence a poor patient outcome, even in patients presenting with early-stage disease. However, the pre-operative diagnosis of STAS remains challenging. With the progress of radiomics-based analyses several attempts have been made to predict STAS based on radiological findings. In the present study, patients with NSCLC which is located peripherally and tumors ≤ 2 cm in size on computed tomography (CT) that were potential candidates for sublobar resection were enrolled in this study. The radiologic features of the targeted tumors on thin-section CT were extracted using the PyRadiomics v3.0 software package, and a predictive model for STAS was built using the t-test and XGBoost. Thirty-five out of 226 patients had a STAS histology. The predictive model of STAS indicated an area under the receiver-operator characteristic curve (AUC) of 0.77. There was no significant difference in the overall survival (OS) for lobectomy between the predicted-STAS (+) and (−) groups (p = 0.19), but an unfavorable OS for sublobar resection was indicated in the predicted-STAS (+) group (p < 0.01). These results suggest that radiomics with machine-learning helped to develop a favorable model of STAS (+) NSCLC, which might be useful for the proper selection of candidates who should undergo sublobar resection.

Residual ctDNA after treatment predicts early relapse in patients with early-stage NSCLC.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8517-8517
Author(s):  
Davina Gale ◽  
Katrin Heider ◽  
Malcolm Perry ◽  
Giovanni Marsico ◽  
Andrea Ruiz-Valdepeñas ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Deep Sequencing ◽  
Early Stage ◽  
Post Treatment ◽  
Disease Stage ◽  
Analytical Sensitivity ◽  
Disease Relapse ◽  
Clinical Progression ◽  
Liquid Biopsies ◽  
Early Stage Disease

8517 Background: Liquid biopsies based on circulating tumor DNA (ctDNA) analysis are being investigated for detection of residual disease and recurrence. Conclusive evidence for utility of ctDNA in early-stage non-small cell lung cancer (NSCLC) is awaited. Due to low ctDNA levels in early-stage disease or post-treatment, effective methods require high analytical sensitivity to detect mutant allele fractions (MAF) below 0.01%. Methods: We analysed 363 plasma samples from 88 patients with NSCLC recruited to the LUng cancer CIrculating tumour DNA (LUCID) study, with disease stage I (49%), II (28%) and III (23%). 62% were adenocarcinomas. Plasma was collected before and after treatment, and at 3, 6 and 9 months after surgery (N = 69) or chemoradiotherapy (N = 19). Additional plasma was collected at disease relapse for 17 patients. Median follow-up was 3 years, and 40 patients progressed or died of any cause. We employed the RaDaR™ assay, a highly sensitive personalized assay using deep sequencing of up to 48 tumor-specific variants. Variants identified by tumor exome analysis were tested by deep sequencing of tumor tissue and buffy coat DNA to verify somatic mutations and exclude clonal hematopoiesis. The RaDaR assay demonstrated 90% sensitivity at 0.001% MAF in analytical validation studies. Results: ctDNA was detected in 26% of samples, at median MAF of 0.047% (range: 0.0007% to > 2%), and prior to treatment in 87%, 77% and 24% for disease stage III, II and I respectively. For 62 patients, plasma was collected at a landmark timepoint, between 2 weeks and 4 months after initial treatment. ctDNA detection at the landmark timepoint was strongly predictive of clinical disease relapse, with Hazard Ratio of 20.7 (CI: 7.7-55.5, p-value < 0.0001). All 11 cases with ctDNA detected at landmark had disease progression, a median of 121 days after detection, and these included all 8 patients that relapsed within 300 days of treatment. Across 27 patients whose disease progressed during the study, ctDNA was detected at any timepoint post-treatment in 17 cases, with a median lead time of 203 days, and up to 741 days prior to clinical progression. ctDNA was detected post-treatment, in 13 of the 15 patients that progressed and had ctDNA detected prior to treatment. Conclusions: Our results support an emerging paradigm shift, by demonstrating that liquid biopsies can reliably detect recurrence of NSCLC at a preclinical stage, many months before clinical progression, thereby offering the opportunity for earlier therapeutic intervention. Clinical trial information: NCT04153526.

The pathway to diagnosis and treatment for surgically managed lung cancer patients

2019 ◽  
Author(s):  
Victoria White ◽  
Rebecca J Bergin ◽  
Robert J Thomas ◽  
Kathryn Whitfield ◽  
David Weller
Keyword(s):  
Lung Cancer ◽  
Primary Care ◽  
Cancer Patients ◽  
Secondary Care ◽  
Primary Care Physicians ◽  
Treatment Time ◽  
Early Stage ◽  
Diagnosis And Treatment ◽  
Early Stage Disease ◽  
Lung Cancer Patients

Abstract Background Most lung cancer is diagnosed at an advanced stage, resulting in poor survival. This study examined diagnostic pathways for patients with operable lung cancer to identify factors contributing to early diagnosis. Methods Surgically treated lung cancer patients (aged ≥40, within 6 months of diagnosis), approached via the population-based Cancer Registry, with their primary care physicians (PCPs) and specialists completed cross-sectional surveys assessing symptoms, diagnostic route (symptomatic or ‘investigation’ of other problem), tests, key event dates and treatment. Time intervals to diagnosis and treatment were determined, and quantile regression examined differences between the two diagnostic routes. Cox proportional hazard regression analyses examined associations between survival and diagnostic route adjusting for stage, sex and age. Results One hundred and ninety-two patients (36% response rate), 107 PCPs and 55 specialists participated. Fifty-eight per cent of patients had a symptomatic diagnostic route reporting an average of 1.6 symptoms, most commonly cough, fatigue or haemoptysis. Symptomatic patients had longer median primary care interval than ‘investigation’ patients (12 versus 9 days, P < 0.05) and were more likely to report their PCP first-ordered imaging tests. Secondary care interval was shorter for symptomatic (median = 43 days) than investigation (median = 62 days, P < 0.05) patients. However, 56% of all patients waited longer than national recommendations (6 weeks). While survival estimates were better for investigation than symptomatic patients, these differences were not significant. Conclusion Many operable lung cancer patients are diagnosed incidentally, highlighting the difficulty of symptom-based approaches to diagnosing early stage disease. Longer than recommended secondary care interval suggests the need for improvements in care pathways.

Immunotherapy and Radiation Therapy for Non-Small Cell Lung Cancer—A Stimulating Partnership

2020 ◽  
Vol 41 (03) ◽  
pp. 360-368
Author(s):  
Ritchell van Dams ◽  
Ye Yuan ◽  
Clifford G. Robinson ◽  
Percy Lee
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Metastatic Disease ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Locally Advanced ◽  
Small Cell ◽  
Standards Of Care ◽  
Small Cell Lung ◽  
Early Stage Disease

AbstractNon-small cell lung cancer (NSCLC) is the most common subtype of lung cancer and the leading cause of cancer-related death. Although durable local control rates are high after surgical resection or definitive radiotherapy for early-stage disease, a substantial proportion of these patients eventually experience regional and/or distant failure and succumb to their metastatic disease. The discovery of immunotherapeutics and targeted biologics has revolutionized the treatment of locally advanced and metastatic disease, improving progression-free and overall survival when incorporated with the current standards of care. Notably, post-hoc analyses and early clinical trials provide a growing body of evidence to support a synergistic effect between radiation and immunotherapy for the treatment of NSCLC from early-stage to metastatic disease. Radiotherapy appears to be capable of not only potentiating the effect of immunotherapy in targeted lesions, but also eliciting an antitumor response in distant lesions without any direct exposure to radiation. This review explores the biologic basis of immunotherapy, targeted biologics, and radiotherapy as well as the preclinical and clinical data that support the combined use of radioimmunotherapy for early-stage, locally advanced, and metastatic NSCLC.

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