scholarly journals Genetic and immunologic features of recurrent stage I lung adenocarcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Johannes R. Kratz ◽  
Jack Z. Li ◽  
Jessica Tsui ◽  
Jen C. Lee ◽  
Vivianne W. Ding ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Early Stage ◽  
Cytolytic Activity ◽  
Stage I ◽  
Study Cohort ◽  
Early Stage Lung Cancer ◽  
Adaptive Immune ◽  
Recurrent Tumors ◽  
Stage Lung Cancer

AbstractAlthough surgery for early-stage lung cancer offers the best chance of cure, recurrence still occurs between 30 and 50% of the time. Why patients frequently recur after complete resection of early-stage lung cancer remains unclear. Using a large cohort of stage I lung adenocarcinoma patients, distinct genetic, genomic, epigenetic, and immunologic profiles of recurrent tumors were analyzed using a novel recurrence classifier. To characterize the tumor immune microenvironment of recurrent stage I tumors, unique tumor-infiltrating immune population markers were identified using single cell RNA-seq on a separate cohort of patients undergoing stage I lung adenocarcinoma resection and applied to a large study cohort using digital cytometry. Recurrent stage I lung adenocarcinomas demonstrated higher mutation and lower methylation burden than non-recurrent tumors, as well as widespread activation of known cancer and cell cycle pathways. Simultaneously, recurrent tumors displayed downregulation of immune response pathways including antigen presentation and Th1/Th2 activation. Recurrent tumors were depleted in adaptive immune populations, and depletion of adaptive immune populations and low cytolytic activity were prognostic of stage I recurrence. Genomic instability and impaired adaptive immune responses are key features of stage I lung adenocarcinoma immunosurveillance escape and recurrence after surgery.

scholarly journals Multiomic Characterization of Stage I Lung Adenocarcinoma Reveals Distinct Genetic and Immunologic Features of Recurrent Disease

2021 ◽  
Author(s):  
Johannes R Kratz ◽  
Jack Z Li ◽  
Jessica Tsui ◽  
Jen C Lee ◽  
Vivianne W Ding ◽  
...  
Keyword(s):  
Lung Cancer ◽  
High Risk ◽  
Lung Adenocarcinoma ◽  
Early Stage ◽  
Stage I ◽  
Early Stage Lung Cancer ◽  
Risk Of Recurrence ◽  
Adaptive Immune ◽  
Mutation Burden ◽  
Lung Adenocarcinomas

Background: Recurrence after surgery for early-stage lung cancer is common, occurring between 30-50% of the time. Despite the popularization of prognostic gene signatures in early-stage lung cancer that allow us to better predict which patients may recur, why patients recur after surgery remains unclear. Methods: Using a large cohort of lung adenocarcinoma patients with complete genetic, genomic, epigenetic and clinical profiling, a recurrence classifier was developed which identifies patients at highest risk of recurrence. The genetic, genomic, and epigenetic profiles of stage I patients with low- vs. high-risk of recurrence were compared. To characterize the tumor immune microenvironment of recurrent stage I tumors, single cell RNA-seq was performed on fresh tissue samples undergoing lung adenocarcinoma resection at UCSF to identify unique immune population markers and applied to the large stage I lung adenocarcinoma cohort using digital cytometry. Results: Recurrence high-risk stage I lung adenocarcinomas demonstrated a higher mutation burden than low-risk tumors, however, none of the known canonical lung cancer driver mutations were more prevalent in high-risk tumors. Transcriptomic analysis revealed widespread activation of known cancer and cell cycle pathways with simultaneous downregulation of immune response pathways including antigen presentation and Th1/Th2 activation. Tumors at high-risk of recurrence displayed depleted adaptive immune populations, and depletion of adaptive immune populations was independently prognostic of recurrence in stage I lung adenocarcinomas. Conclusion: Recurrent stage I lung adenocarcinomas display distinct features of genomic and genetic instability including increased tumor mutation burden, neoantigen load, activation of numerous mitotic and cell cycle genes, and decreased genome-wide methylation burden. Relative depletion of infiltrating adaptive immune populations may allow these tumors to escape immunosurveillance and recur after surgery.

scholarly journals Management of patients with early stage lung cancer – why do some patients not receive treatment with curative intent?

2020 ◽  
Author(s):  
Ross Lawrenson ◽  
Chunhuan Lao ◽  
Leonie Brown ◽  
Lucia Moosa ◽  
Lynne Chepulis ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Early Stage ◽  
Hazard Ratio ◽  
Stage I ◽  
Curative Treatment ◽  
Curative Surgery ◽  
Early Stage Lung Cancer ◽  
Curative Intent ◽  
Receive Treatment ◽  
Stage Lung Cancer

Abstract Backgrounds This study aims to understand the factors that influence whether patients receive potentially curative treatment for early stage lung cancer. Methods Patients included those diagnosed with early stage lung cancer in 2011-2018 and resident in the New Zealand Midland Cancer Network region. Logistic regression model was used to estimate the odds ratios of having curative surgery/ treatment. The Kaplan Meier method was used to examine the all-cause survival and Cox proportional hazard model was used to estimate the hazard ratio of death. Results In total 419/583 (71.9%) of patients with Stage I and II disease were treated with curative intent - 272 (46.7%) patients had curative surgery. Patients not receiving potentially curative treatment were older, were less likely to have non-small cell lung cancer (NSCLC), had poorer lung function and were more likely to have an ECOG performance status of 2+. Current smokers were less likely to be treated with surgery and more likely to receive treatment with radiotherapy and chemotherapy. Those who were treated with surgery had a 2-year survival of 87.8% (95% CI: 83.8%-91.8%) and 5-year survival of 69.6% (95% CI: 63.2%-76.0%). Stereotactic ablative body radiotherapy (SABR) has equivalent effect on survival compared to curative surgery (hazard ratio: 0.77, 95% CI: 0.37-1.61). Conclusions The majority of patients with stage I and II lung cancer are managed with potentially curative treatment – mainly surgery and increasingly with SABR. The outcomes of those being diagnosed with stage I and II disease and receiving treatment is positive with 70% surviving 5 years.

Photodynamic therapy using Laserphyrin for centrally located early stage lung cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7229-7229 ◽  
Author(s):  
J. Usuda ◽  
H. Kato ◽  
T. Okunaka ◽  
K. Furukawa ◽  
H. Honda ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Photodynamic Therapy ◽  
Early Stage ◽  
Stage I ◽  
University Hospital ◽  
Early Stage Lung Cancer ◽  
Endobronchial Ultrasonography ◽  
Tokyo Medical ◽  
Medical University ◽  
Stage Lung Cancer

7229 Background: In central type early stage lung cancer, the tumor must be located only as far as the segmental bronchi and be carcinoma in situ or with only limited invasion into the bronchial wall. Laserphyrin (mono-L-aspartyl chlorine e6, NPe6) is a second generation photosensitize and approved by the Japanese government and has been on sale from June 2004. Methods: Four h after the administration of Laserphyrin 40 mg/m2, we irradiated using diode laser (100 mJ/cm2). Before PDT, we evaluated the tumor lesions and tumor depth using autofluorescence bronchoscopy and endobronchial ultrasonography (EBUS), and we confirmed the area of laser irradiation. Results: From February 1980 to December 2005, a total number of 204 patients with 264 lesions of centrally located early stage lung cancer underwent photodynamic therapy (PDT) in the Department of Thoracic Surgery, Tokyo Medical University Hospital. There were 185 clinical stage 0 lesions and 79 stage I lesions. CRs and PRs were obtained in 224 lesions (84.8%) and 40 lesions (15.2%) out of 264 lesions. From July 2004 to December 2005, we performed Laserphyrin-PDT for 28 lesions of centrally located early stage lung cancer in Tokyo Medical University Hospital. The rate of CR was 92.9% (26 lesions) in 28 lesions. For Laserphyrin-PDT, Skin photosensitivity was very low and the clean-up bronchoscopies were not frequently needed, and the period of hospitalization was shorter compared to that for Photofrin-PDT. Conclusions: We conclude that PDT using Laserphyrin will be a standard option for stage 0 (TisN0M0) and stage I (T1N0M0) centrally located early stage lung cancer. No significant financial relationships to disclose.

Genomic profiling of early-stage lung cancer for patterns of recurrence.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23126-e23126
Author(s):  
Costanzo A DiPerna ◽  
Leah Fine
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Early Stage ◽  
Molecular Profiling ◽  
Stage I ◽  
Genomic Profiling ◽  
Early Stage Lung Cancer ◽  
Lung Cancer Patients ◽  
Adjuvant Therapies ◽  
Stage Lung Cancer

e23126 Background: Currently there is no evidence to support molecular profiling for early stage resected lung cancer patients. However, up to 50% of patients experience recurrence following resection. This is a first-of-a-kind study utilizing comprehensive genomic profiling technology to characterize genomic patterns for risk of recurrence in early stage lung cancer patients within the community hospital setting who have undergone lung surgery. Methods: A total of 60 Stage I-II lung cancer patients, all having undergone pulmonary resection, were evaluated with molecular profiling of their primary lung cancer tissue using Foundation Medicine’s FoundationOneÒ test. Patient age in years ranged from 39-86, and all patients were confirmed Stage I or II based on final pathologic analysis. Samples were taken from three community hospitals that are part of the Addario Lung Cancer Foundation Centers of Excellence program. Patients whose tumors were resected between the years of 2009-2017 were included in this combined retrospective and prospective study. Results: More than 300 genes were evaluated using FoundationOneÒ and patients were segmented to establish similarities and differences. Analysis of segments include gender, recurrence, smoking status among others. Gene patterns across segments are beginning to reveal possible predictive profiles. Final analysis will be completed shortly. Conclusions: Genomic profiling could help predict lung cancer recurrence for early stage lung cancer patients. Similarities amongst patients with recurrences imply that early genomic profiling of lung cancer patients could help predict those patients who would benefit from adjuvant therapies including conventional chemotherapy. Genomic profiling for early stage lung cancer should be studied further and in greater detail to help predict those patients who would benefit from potentially early adjuvant therapies.

Circulating tumor DNA (ctDNA) mutation and epigenomic patterns in early-stage lung cancer patients and its utility in identifying patients at high risk for early recurrence.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14557-e14557
Author(s):  
Jong Ho Cho ◽  
Il-Jin Kim ◽  
Junghee Lee ◽  
Hong Kwan Kim ◽  
Jinseon Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Somatic Mutations ◽  
Early Stage ◽  
Circulating Tumor Dna ◽  
Stage I ◽  
Early Stage Lung Cancer ◽  
Lung Cancer Patients ◽  
Tumor Dna ◽  
Stage Lung Cancer

e14557 Background: Circulating tumor DNA (ctDNA) analysis has been successfully applied to therapy selection and treatment monitoring in advanced cancer patients. However, it is not yet established whether ctDNA can be used clinically for early cancer detection or predicting tumor recurrence in early stage lung cancer patients. Methods: We analyzed pre-operative plasma samples from 55 early stage NSCLC patients (stages I-IIIA) using next-generation sequencing to detect somatic mutations and differential epigenomics patterns, including methylation signatures. Results: Using somatic mutation analysis alone, ctDNA was detected in 42% (23/55) of patients, whereas combined mutational and epigenomic analysis detected ctDNA in 71%. ctDNA detection rate also varied markedly between lung squamous cell carcinoma (SCC) and adenocarcinoma (ADC);using combined analysis of somatic mutations and epigenomic patterns, ctDNA was detected in all SCC patients, while only 55% of ADC (12/22) were ctDNA-positive (p= 0.006). Within the ADC subgroup, ctDNA detection rates using the combined approach were dependent on disease stage: 47% (8/17) in stage I, 100% (2/2) in stage II, and 100% (2/2) in stage IIIA. Importantly, pre-operative ctDNA status was correlated with tumor recurrence post-resection; three of eight (38%) ctDNA-positive stage I ADC patients recurred within 2 years of resection, while only one of nine (11%) ctDNA-negative stage I ADC patients recurred (p= 0.29). Conclusions: Taken together, we show that the combination of somatic mutation detection and epigenomic analysis outperforms each individual biomarker in the detection of ctDNA in early stage lung cancer. Importantly, we also demonstrate that pre-operative ctDNA detection may identify a high-risk population of early stage lung cancer patients that may benefit from (neo)adjuvant therapy.

scholarly journals Quantification of CYFRA 21-1 and a CYFRA 21-1–anti-CYFRA 21-1 autoantibody immune complex for detection of early stage lung cancer

2019 ◽  
Vol 55 (68) ◽  
pp. 10060-10063 ◽  
Author(s):  
Keum-Soo Song ◽  
Satish Balasaheb Nimse ◽  
Shrikant Dashrath Warkad ◽  
Ae-Chin Oh ◽  
Taisun Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune Complex ◽  
Early Stage ◽  
Population Based ◽  
Stage I ◽  
Early Stage Lung Cancer ◽  
Stage I Lung Cancer ◽  
Stage Lung Cancer

Population-based screening of stage 0–I lung cancer is crucial for saving lives. The CIC/CYFRA 21-1 ratio allows the detection of stage I lung cancer with 76.0% sensitivity and 87.5% specificity.

Automated imaging-based stratification of early-stage lung cancer patients prior to receiving surgical resection using deep learning applied to CTs.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1552-1552
Author(s):  
Felipe Soares Torres ◽  
Shazia Akbar ◽  
Srinivas Raman ◽  
Kazuhiro Yasufuku ◽  
Felix Baldauf-Lenschen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Deep Learning ◽  
Cancer Patients ◽  
Surgical Resection ◽  
Mortality Risk ◽  
Early Stage ◽  
Stage I ◽  
Early Stage Lung Cancer ◽  
Lung Cancer Patients ◽  
Stage Lung Cancer

1552 Background: Computed tomography (CT) imaging is an important tool to guide further investigation and treatment in patients with lung cancer. For patients with early stage lung cancer, surgery remains an optimal treatment option. Artificial intelligence applied to pretreatment CTs may have the ability to quantify mortality risk and stratify patients for more individualized diagnostic, treatment and monitoring decisions. Methods: A fully automated, end-to-end model was designed to localize the 36cm x 36cm x 36cm space centered on the lungs and learn deep prognostic features using a 3-dimensional convolutional neural network (3DCNN) to predict 5-year mortality risk. The 3DCNN was trained and validated in a 5-fold cross-validation using 2,924 CTs of 1,689 lung cancer patients from 6 public datasets made available in The Cancer Imaging Archive. We evaluated 3DCNN’s ability to stratify stage I & II patients who received surgery into mortality risk quintiles using the Cox proportional hazards model. Results: 260 of the 1,689 lung cancer patients in the withheld validation dataset were diagnosed as stage I or II, received a surgical resection within 6 months of their pretreatment CT and had known 5-year disease and survival outcomes. Based on the 3DCNN’s predicted mortality risk, patients in the highest risk quintile had a 14.2-fold (95% CI 4.3-46.8, p < 0.001) increase in 5-year mortality hazard compared to patients in the lowest risk quintile. Conclusions: Deep learning applied to pretreatment CTs provides personalised prognostic insights for early stage lung cancer patients who received surgery and has the potential to inform treatment and monitoring decisions.[Table: see text]

scholarly journals Management of patients with early stage lung cancer – why do some patients not receive treatment with curative intent?

2020 ◽  
Author(s):  
Ross Lawrenson ◽  
Chunhuan Lao ◽  
Leonie Brown ◽  
Lucia Moosa ◽  
Lynne Chepulis ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Early Stage ◽  
Stage I ◽  
Curative Treatment ◽  
Curative Surgery ◽  
Early Stage Lung Cancer ◽  
Curative Intent ◽  
Receive Treatment ◽  
To Receive ◽  
Stage Lung Cancer

Abstract Backgrounds This study aims to understand the factors that influence whether patients receive potentially curative treatment for early stage lung cancer. A key question was whether indigenous Māori patients were less likely to receive treatment. Methods Patients included those diagnosed with early stage lung cancer in 2011-2018 and resident in the New Zealand Midland Cancer Network region. Logistic regression model was used to estimate the odds ratios of having curative surgery/ treatment. The Kaplan Meier method was used to examine the all-cause survival and Cox proportional hazard model was used to estimate the hazard ratio of death. Results In total 419/583 (71.9%) of patients with Stage I and II disease were treated with curative intent - 272 (46.7%) patients had curative surgery. Patients not receiving potentially curative treatment were older, were less likely to have non-small cell lung cancer (NSCLC), had poorer lung function and were more likely to have an ECOG performance status of 2+. Current smokers were less likely to be treated with surgery and more likely to receive treatment with radiotherapy and chemotherapy. Those who were treated with surgery had a 2-year survival of 87.8% (95% CI: 83.8%-91.8%) and 5-year survival of 69.6% (95% CI: 63.2%-76.0%). Stereotactic ablative body radiotherapy (SABR) has equivalent effect on survival compared to curative surgery (hazard ratio: 0.77, 95% CI: 0.37-1.61). After adjustment we could find no difference in treatment and survival between Māori and non-Māori. Conclusions The majority of patients with stage I and II lung cancer are managed with potentially curative treatment – mainly surgery and increasingly with SABR. The outcomes of those being diagnosed with stage I and II disease and receiving treatment is positive with 70% surviving 5 years.

Outcomes of early stage lung cancer treatments in older patients: A SEER database analysis.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7571-7571 ◽  
Author(s):  
Alissa S. Marr ◽  
Valerie Shostrom ◽  
K. M Islam ◽  
Apar Kishor Ganti
Keyword(s):  
Lung Cancer ◽  
Older Patients ◽  
Early Stage ◽  
Age Groups ◽  
Stage I ◽  
Seer Database ◽  
Cancer Specific Survival ◽  
Early Stage Lung Cancer ◽  
Younger Patients ◽  
Stage Lung Cancer

7571 Background: Although the majority of lung cancer patients are over the age of 65, there are limited data on outcomes of treatment options for early stage lung cancer in older patients. Methods: Treatment and outcome data of stage I and II non-small cell lung cancer (NSCLC) patients were obtained from the Surveillance, Epidemiology and End Results (SEER) database. Treatment modalities included no treatment, surgery, radiation, and a combination of surgery and radiation. Patients were divided based on age groups into <65, 65-75, and >75 years old. Multivariate logistic regression was used to compare the likelihood of survival in the three age groups while controlling for gender and race. Results: A total of 10,763 patients diagnosed with stage I and II NSCLC between 1988 and 2007 within the SEER database were analyzed. The age distribution was as follows: <65 (n=3558), 65-75 years (n= 4454), >75 years (n=2751). Patients <65 years of age were more likely than those >75 years of age to be treated with surgery (72.5% vs. 53.5%, respectively; p = <0.0001). Patients >75 years of age were more often treated with radiation alone (23%) or no treatment (18.2%) as compared to those patients <65 (9% and 4.9%, respectively; p = <0.0001). Patients <65 years of age with stage I lung cancer had a statistically significant improved lung cancer-specific 5-year survival with surgery alone as compared to those 65-75 years and >75 years. Lung cancer specific mortality at 5 years was 19%, 26% and 30%, respectively; p= <0.0001. Similar results were seen in stage II patients. When stage I patients received radiation therapy, lung cancer-specific deaths at 5 years were not different between the three groups (66% vs. 63% vs. 66%, respectively; p=0.1263). The 5-year lung cancer- related mortality was lower in younger patients who received no treatment (51% in <65, 56% in 65-75, and 57% in >75 years old; p=0.006). Conclusions: Older patients treated surgically for stages I and II NSCLC have a lower lung cancer-specific survival when compared to younger patients. In contrast, there is no difference in lung cancer-specific survival for patients treated with radiation therapy. Hence, careful selection of older patients for surgical therapy of early stage NSCLC is warranted.

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