scholarly journals Immune Escape Mechanisms in Non Small Cell Lung Cancer

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3605
Author(s):  
Andrea Anichini ◽  
Valentina E. Perotti ◽  
Francesco Sgambelluri ◽  
Roberta Mortarini
Keyword(s):  
Lung Cancer ◽  
Immune Evasion ◽  
Immune Escape ◽  
Early Stage ◽  
Human Leukocyte ◽  
Immune Checkpoint Blockade ◽  
Immune Checkpoints ◽  
Normal Lung ◽  
Early Stage Nsclc ◽  
Immune Escape Mechanisms

Development of strong immune evasion has been traditionally associated with the late stages of solid tumor progression, since advanced cancers are more likely to have reached the third phase of the immunoediting process. However, by integrating a variety of approaches, evidence for active immune escape mechanisms has been found even in the pre-invasive lesions that later progress to the main NSCLC histotypes. Pre-invasive lesions of adenocarcinoma (LUAD) and of squamous cell carcinoma (LUSC) can show impaired antigen presentation, loss of heterozygosity at the Human Leukocyte Antigen (HLA) region, neoantigen silencing, activation of immune checkpoints, altered TH1/TH2 cytokine ratios, and immune contexture evolution. Analysis of large panels of LUAD vs. LUSC, of early stage NSCLC vs. normal lung tissue, of specific molecular subsets of NSCLC, and of distinct regions within the same tumor, indicates that all these processes of immune escape continue to evolve in the invasive stage of NSCLC, are associated with inter- and intra-tumor heterogeneity, and contribute to resistance to therapy by immune checkpoint blockade (ICB). In this review, we will discuss the most recent evidence on immune escape mechanisms developing from the precursor to invasive stage in NSCLC, and the contribution of immune evasion to resistance to ICB in lung cancer.

scholarly journals Comparison of Oncologic Outcomes between Carbon Ion Radiotherapy and Stereotactic Body Radiotherapy for Early-Stage Non-Small Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 176
Author(s):  
Yuhei Miyasaka ◽  
Shuichiro Komatsu ◽  
Takanori Abe ◽  
Nobuteru Kubo ◽  
Naoko Okano ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Propensity Score ◽  
Small Cell Lung Cancer ◽  
Stereotactic Body Radiotherapy ◽  
Early Stage ◽  
Small Cell ◽  
Oncologic Outcomes ◽  
Comparison Study ◽  
Small Cell Lung ◽  
Early Stage Nsclc

Lung cancer is a leading cause of cancer-related deaths worldwide. Radiotherapy is an essential treatment modality for inoperable non-small cell lung cancer (NSCLC). Stereotactic body radiotherapy (SBRT) is the standard treatment for early-stage NSCLC because of its favorable local control (LC) compared to conventional radiotherapy. Carbon ion radiotherapy (CIRT) is a kind of external beam radiotherapy characterized by a steeper dose distribution and higher biological effectiveness. Several prospective studies have shown favorable outcomes. However, there is no direct comparison study between CIRT and SBRT to determine their benefits in the management of early-stage NSCLC. Thus, we conducted a retrospective, single-institutional, and contemporaneous comparison study, including propensity score-adjusted analyses, to clarify the differences in oncologic outcomes. The 3-year overall survival (OS) was 80.1% in CIRT and 71.6% in SBRT (p = 0.0077). The 3-year LC was 87.7% in the CIRT group and 79.1% in the SBRT group (p = 0.037). Multivariable analyses showed favorable OS and LC in the CIRT group (hazard risk [HR] = 0.41, p = 0.047; HR = 0.30, p = 0.040, respectively). Log-rank tests after propensity score matching and Cox regression analyses using propensity score confirmed these results. These data provided a positive efficacy profile of CIRT for early-stage NSCLC.

scholarly journals Circulating serum exosomal miR-20b-5p and miR-3187-5p as efficient diagnostic biomarkers for early-stage non-small cell lung cancer

2020 ◽  
Vol 245 (16) ◽  
pp. 1428-1436
Author(s):  
Zhi-Jun Zhang ◽  
Xing-Guo Song ◽  
Li Xie ◽  
Kang-Yu Wang ◽  
You-Yong Tang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Small Cell ◽  
Small Cell Lung ◽  
Diagnostic Biomarkers ◽  
Non Invasive ◽  
Early Stage Nsclc ◽  
Nsclc Patients

Circulating exosomal microRNAs (ExmiRNAs) provide an ideal non-invasive method for cancer diagnosis. In this study, we evaluated two circulating ExmiRNAs in NSCLC patients as a diagnostic tool for early-stage non-small lung cancer (NSCLC). The exosomes were characterized by qNano, transmission electron microscopy, and Western blot, and the ExmiRNA expression was measured by microarrays. The differentially expressed miRNAs were verified by RT-qPCR using peripheral blood specimens from NSCLC patients ( n = 276, 0 and I stage: n = 104) and healthy donors ( n = 282). The diagnostic values were measured by receiver operating characteristic (ROC) analysis. The results show that the expression of both ExmiR-20b-5p and ExmiR-3187-5p was drastically reduced in NSCLC patients. The area under the ROC curve (AUC) was determined to be 0.818 and 0.690 for ExmiR-20b-5p and ExmiR-3187-5p, respectively. When these two ExmiRNAs were combined, the AUC increased to 0.848. When the ExmiRNAs were administered with either carcinoembryonic antigen (CEA) or cytokeratin-19-fragment (CYFRA21-1), the AUC was further improved to 0.905 and 0.894, respectively. Additionally, both ExmiR-20b-5p and ExmiR-3187-5p could be used to distinguish early stages NSCLC (0 and I stage) from the healthy controls. The ROC curves showed that the AUCs were 0.810 and 0.673, respectively. Combination of ExmiR-20b-5p and ExmiR-3187-5p enhanced the AUC to 0.838. When CEA and CYFRA21-1 were administered with the ExmiRNAs, the AUCs were improved to 0.930 and 0.928, respectively. In summary, circulating serum exosomal miR-20b-5p and miR-3187-5p could be used as effective, non-invasive biomarkers for the diagnosis of early-stage NSCLC, and the effects were further improved when the ExmiRNAs were combined. Impact statement The high mortality of non-small cell lung cancer (NSCLC) is mainly because the cancer has progressed to a more advanced stage before diagnosis. If NSCLC can be diagnosed at early stages, especially stage 0 or I, the overall survival rate will be largely improved by definitive treatment such as lobectomy. We herein validated two novel circulating serum ExmiRs as diagnostic biomarkers for early-stage NSCLC to fulfill the unmet medical need. Considering the number of specimens in this study, circulating serum exosomal miR-20b-5p and miR-3187-5p are putative NSCLC biomarkers, which need to be further investigated in a larger randomized controlled clinical trial.

scholarly journals Genome-Wide Analysis of Survival in Early-Stage Non–Small-Cell Lung Cancer

2009 ◽  
Vol 27 (16) ◽  
pp. 2660-2667 ◽  
Author(s):  
Yen-Tsung Huang ◽  
Rebecca S. Heist ◽  
Lucian R. Chirieac ◽  
Xihong Lin ◽  
Vidar Skaug ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Massachusetts General Hospital ◽  
Early Stage ◽  
The United States ◽  
Small Cell ◽  
Genome Wide Analysis ◽  
Early Stage Nsclc ◽  
Genome Wide ◽  
Nsclc Patients

Purpose Lung cancer, of which 85% is non–small-cell (NSCLC), is the leading cause of cancer-related death in the United States. We used genome-wide analysis of tumor tissue to investigate whether single nucleotide polymorphisms (SNPs) in tumors are prognostic factors in early-stage NSCLC. Patients and Methods One hundred early-stage NSCLC patients from Massachusetts General Hospital (MGH) were used as a discovery set and 89 NSCLC patients collected by the National Institute of Occupational Health, Norway, were used as a validation set. DNA was extracted from flash-frozen lung tissue with at least 70% tumor cellularity. Genome-wide genotyping was done using the high-density SNP chip. Copy numbers were inferred using median smoothing after intensity normalization. Cox models were used to screen and validate significant SNPs associated with the overall survival. Results Copy number gains in chromosomes 3q, 5p, and 8q were observed in both MGH and Norwegian cohorts. The top 50 SNPs associated with overall survival in the MGH cohort (P ≤ 2.5 × 10−4) were selected and examined using the Norwegian cohort. Five of the top 50 SNPs were validated in the Norwegian cohort with false discovery rate lower than 0.05 (P < .016) and all five were located in known genes: STK39, PCDH7, A2BP1, and EYA2. The numbers of risk alleles of the five SNPs showed a cumulative effect on overall survival (Ptrend = 3.80 × 10−12 and 2.48 × 10−7 for MGH and Norwegian cohorts, respectively). Conclusion Five SNPs were identified that may be prognostic of overall survival in early-stage NSCLC.

scholarly journals Stereotactic body radiation therapy versus surgery for patients with early-stage non–small cell lung cancer( ≤ 5cm): A systematic review and meta-analysis

2021 ◽  
Author(s):  
Yueling Zhou ◽  
Ping Wen ◽  
Yue Yu ◽  
Zhenyi Yang ◽  
Yixuan Luo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Radiation Therapy ◽  
Stereotactic Body Radiation Therapy ◽  
Early Stage ◽  
Meta Analysis ◽  
Small Cell ◽  
Survival Outcomes ◽  
Small Cell Lung ◽  
Early Stage Nsclc

Abstract Background: Stereotactic body radiation therapy (SBRT) is considered as the preferred treatment method for inoperable early-stage non-small cell lung cancer (NSCLC). However, there is still a debate on the efficacy of SBRT and surgery. This meta-analysis aimed to compare survival outcomes of SBRT and surgery for early-stage NSCLC (≤5cm).Methods: A systematic review and meta-analysis were performed to compare survival outcomes of surgery and SBRT. And the pooled analysis was conducted with STATA 14.0 software. Results: Thirty-nine comparative studies were included for systematic review and twenty-eight of which for quantitative analysis. Compared with SBRT, overall survival (OS) was superior after surgical resection, included lobectomy, sublobar resection, video-assisted thoracoscopic surgery, and thoracotomy, for patients with early-stage NSCLC (≤5cm). And the results of subgroup analysis remained the support of surgery except for the OS of operable matched cohorts and the one matched cohort of age ≥75. However, the HR of OS showed a reduction from patients with unspecific age, ≥65 to ≥75 years old and histopathologically confirmed NSCLC to clinical NSCLC. Although cancer-specific survival and local control was superior after surgery, the recurrence rate of tumors, locoregional control, distant control, and regional control of matched patients demonstrated no significantly different outcomes between SBRT and surgery for early-stage NSCLC.Conclusions: Results show that surgery has superior OS, CSS and local control compared to SBRT for early-stage NSCLC. There is still necessary to explore the survival difference between SBRT and surgery for patients with different characteristics by large-sample, long-term follow-up randomized clinical studies.

Surgical outcomes for early-stage non-small cell lung cancer at facilities with stereotactic body radiation therapy programs.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8538-8538
Author(s):  
Yusef Syed ◽  
William A. Stokes ◽  
Onkar Khullar ◽  
Nikhil Sebastian ◽  
Manali Rupji ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Radiation Therapy ◽  
Stereotactic Body Radiation Therapy ◽  
Operative Mortality ◽  
Early Stage ◽  
Mortality Rates ◽  
Small Cell ◽  
Small Cell Lung ◽  
Early Stage Nsclc ◽  
Interaction Testing

8538 Background: Patients undergoing surgery for early-stage non-small cell lung cancer (NSCLC) may be at high-risk for post-operative mortality. Access to stereotactic body radiation therapy (SBRT) offers a less invasive alternative for this population that may facilitate more appropriate patient selection for surgery. Methods: An analysis of all patients with early-stage NSCLC reported to the National Cancer Database between 2004-2015 was performed. Post-operative mortality rates were derived using vital status data. Utilization of SBRT was defined by each facility’s SBRT Experience in years and SBRT-to-Surgery volume ratios, defined by quartiles. Multivariable logistic regression with backward elimination was used to test for independence of associations between exposures of interest and post-operative mortality. Interaction testing was performed to assess the statistical relationship of covariates found to have independent associations. Results: The study cohort consisted of 202,542 patients who underwent surgical resection of clinical stage T1-T2 NSCLC (AJCC 7th edition). The 90-day post-operative mortality rate declined significantly during the study period from 4.6% to 2.6% (p < 0.001). During this period, the proportion of facilities that utilized SBRT increased from 3.3% to 77.5% (p < 0.001) and the proportion of patients treated with SBRT increased significantly from 0.7% to 15.4% (p < 0.001). Lower 90-day post-operative mortality rates were observed at facilities with greater than six years of SBRT experience (OR 0.84, CI 0.76-0.94, p = 0.003) and SBRT-to-Surgery volume ratios above 17% (OR 0.85, CI 0.79-0.92, p < 0.001). Additional covariates associated with 90-day mortality included higher surgical volume, geographic region, year of diagnosis, age, sex, race, insurance status, facility type, Charlson-Deyo score, clinical T stage, histology, anatomic location, surgery type, and prior malignancy. Interaction testing between these covariates was negative, demonstrating that higher SBRT Experience and SBRT-to-Surgery volume ratios were independently associated with lower 90-day surgical mortality. Conclusions: Patients who underwent surgery for early-stage NSCLC at facilities with higher SBRT Experience and SBRT-to-Surgery volume ratios had lower rates of post-operative mortality. These findings suggest that the availability of SBRT may be a surrogate for a more comprehensive and safer approach to matching patients to surgery or SBRT. The observation of higher post-operative mortality rates at facilities without an SBRT program deserves further study.

scholarly journals Stereotactic body radiation therapy for early-stage non–small-cell lung cancer in octogenarians and older: an alternative treatment

2020 ◽  
Vol 61 (4) ◽  
pp. 586-593
Author(s):  
Yanping Bei ◽  
Naoya Murakami ◽  
Yuko Nakayama ◽  
Kae Okuma ◽  
Tairo Kashihara ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Radiation Therapy ◽  
Stereotactic Body Radiation Therapy ◽  
Early Stage ◽  
Small Cell ◽  
Recurrence Free Survival ◽  
Small Cell Lung ◽  
Free Survival ◽  
Early Stage Nsclc ◽  
Lung Sbrt

ABSTRACT Surgery is the standard modality for early-stage I–II non-small-cell lung cancer (NSCLC). Generally, patients who are &gt;80 years old tend to have more comorbidities and inferior physical status than younger patients. Stereotactic body radiation therapy (SBRT) may provide an alternative treatment for this group of patients. Here, we report our experience using SBRT to in the management of early-stage NSCLC in patients &gt;80 years old. Patients aged ≥80 years old who were diagnosed with early-stage NSCLC and treated with definitive lung SBRT from January 2000 to January 2018 were retrospectively analysed. Local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), cancer-specific survival (CSS), progression-free survival (PFS), overall survival (OS) and treatment-related toxicities were analysed for patients &gt;80 years old. A total of 153 patients were included, with a median age of 85 years (range, 80–94). The median follow-up period and OS was 39.8 months (range, 10–101 months) and 76 months, respectively. The 3-year OS, PFS, CSS, RRFS and LRFS were 65.3, 58.0, 75.7, 73.9 and 85.3%, respectively. Radiation pneumonitis grade 0–1, grade 2, grade 3 and grade 4 was observed in 135 (88.2%), 13 (8.5%), 4 (2.61%) and 1 (0.6%) patient(s), respectively. On multivariate analyses, tumor size, pretreatment C-reactive protein (CRP) value, histology and pretreatment physical state were significantly associated with OS. Definitive lung SBRT appears to have high LRFS and OS without causing high-grade radiation-related toxicities in early-stage NSCLC patients who were &gt;80 years old.

scholarly journals Reduction of Elevated Plasma Osteopontin Levels With Resection of Non–Small-Cell Lung Cancer

2010 ◽  
Vol 28 (6) ◽  
pp. 936-941 ◽  
Author(s):  
Justin D. Blasberg ◽  
Harvey I. Pass ◽  
Chandra M. Goparaju ◽  
Raja M. Flores ◽  
Suzie Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Small Cell ◽  
Enzyme Linked Immunosorbent Assay ◽  
Small Cell Lung ◽  
Early Stage Nsclc ◽  
Independent Cohort

Purpose Plasma osteopontin (OPN) levels in advanced non–small-cell lung cancer (NSCLC) correlate with therapeutic response and survival, but the utility of plasma OPN for diagnosis and monitoring of early-stage NSCLC has not been investigated. We hypothesize that plasma OPN levels are elevated in early-stage NSCLC and decrease with resection. Patients and Methods Presurgery plasma OPN levels (in ng/mL) were measured by enzyme-linked immunosorbent assay (ELISA) in a discovery set of 60 patients with early-stage NSCLC and were compared with data from 56 cancer-free smokers. Presurgery OPN was validated in an independent cohort of 96 patients with resectable NSCLC. The presurgery levels in the latter cohort were compared with matched postsurgery levels. Perioperative OPN levels were correlated with demographics, tumor characteristics, and perioperative events. OPN was monitored during follow-up. Results Discovery set presurgery NSCLC OPN (271 ± 31 ng/mL) was higher than smokers (40 ± 2 ng/mL; P = .001). Presurgery OPN was similar in the NSCLC validation cohort (324 ng/mL ± 20 ng/mL; P = .134). Postsurgery OPN (256 ng/mL ± 21 ng/mL) measured at mean of 9.8 weeks (range, 2 to 46 weeks) was lower than presurgery OPN (P = .005). Time from surgery significantly impacted postsurgery OPN: OPN ≤ 6 weeks postsurgery (303 n/mL ± 26 ng/mL) was higher than OPN greater than 6 weeks postsurgery (177 ng/mL ± 29 ng/mL; P = .003). Multivariate analysis noted correlations between albumin and creatinine to presurgery OPN and use of thoracotomy to postsurgery OPN. Recurrence rate was 5% at 29 weeks mean follow-up. OPN at recurrence was elevated from postsurgery nadir. Conclusion Plasma OPN levels are elevated in early-stage NSCLC. They are reduced after resection and appear to increase with recurrence. Plasma OPN may have utility as a biomarker in early-stage NSCLC.

scholarly journals Microwave Ablation in Primary Lung Malignancies

2019 ◽  
Vol 36 (04) ◽  
pp. 326-333 ◽  
Author(s):  
Amgad M. Moussa ◽  
Etay Ziv ◽  
Stephen B. Solomon ◽  
Juan C. Camacho
Keyword(s):  
Lung Cancer ◽  
Treatment Option ◽  
Microwave Ablation ◽  
Checkpoint Inhibitors ◽  
Early Stage ◽  
Current Evidence ◽  
Percutaneous Ablation ◽  
Early Stage Disease ◽  
Early Stage Nsclc ◽  
Lung Malignancies

AbstractLung cancer is the leading cause of cancer-related mortality worldwide. Eighty-five percent of cases correspond to non-small cell lung cancer (NSCLC) and pivotal nonsurgical options for early-stage disease include percutaneous ablation and stereotactic body radiation therapy (SBRT). Microwave Ablation (MWA) is a locoregional treatment option that has many advantages over radiofrequency ablation and has been able to overcome the limitations of this technique in the treatment of early-stage NSCLC. In this review article, we highlight the current evidence supporting the use of MWA in patients with early-stage NSCLC and discuss the technical considerations of the procedure, including optimal patient selection and planning strategies, as well as the potential complications and reported outcomes. Finally, we mention future trends involving ablation in NSCLC, including its role in combination with SBRT in central tumors, management of post-SBRT local recurrence, and its potential as an adjuvant treatment option for patients with resistance to systemic therapy or in combination with checkpoint inhibitors.

Barriers for accrual to clinical trials in adult patients (pts) with thoracic malignancies

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6058-6058
Author(s):  
M. Q. Baggstrom ◽  
E. Gilstrap ◽  
A. Skelton ◽  
A. Viswanathan ◽  
D. Morgensztern ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Esophageal Cancer ◽  
Early Stage ◽  
Small Cell ◽  
Advanced Esophageal Cancer ◽  
Small Cell Lung ◽  
Early Stage Nsclc ◽  
Thoracic Malignancies ◽  
Morbid Conditions

6058 Background: Despite recent advances in the treatment of pts with thoracic malignancies, the outcome continues to be poor. Only about 3% of all adult oncology pts enroll in clinical trials compared to approximately 50% of pediatric pts. The proportion of adult pts enrolled in clinical trials is low, even in tertiary cancer centers. It is critical to understand the barriers for accrual to clinical trials. Methods: We reviewed the outpatient charts of all pts with thoracic malignancies (non-small cell lung cancer [NSCLC], small cell lung cancer, and esophageal cancer) referred to the thoracic medical oncology group at our institution from 11/1/2004 to 10/31/2005. Available and appropriate clinical trials are presented to the pts routinely and reasons for non-enrollment are documented. We collected information on histology, stage, performance status (PS) and co-morbid conditions. Appropriate studies at the time of initial consultation were noted from database. Results: Of 284 consecutive patient charts reviewed, 13 pts (4.6%) did not require therapy, 6 pts (2.1%) were deemed to have a non-thoracic primary on review, and 15 pts (5.3%) had already initiated therapy at the time of consultation. Of the remaining 250 evaluable pts, 88 pts (35.2%) were not enrolled because of lack of available appropriate clinical trials at the time of initial consultation. The most common categories were adjuvant therapy for early stage NSCLC and advanced esophageal cancer. Twenty-one pts (8.4%) enrolled onto a clinical trial. The most common reasons for not participating in a clinical trial include: ineligibility due to PS (28 pts, 11.2%), geographic issues (23 pts, 9.2%), patient refusal (16 pts, 6.4%) and co-morbid conditions (9 pts, 3.6%). Ten pts (4.0%) were lost to follow up. Conclusions: 1. Lack of appropriate and available clinical trials and poor PS are the two most common reasons for lack of patient enrollment in clinical trials at our institution. 2. It is critical to develop innovative clinical trials for pts with advanced esophageal cancer, adjuvant therapy in early stage NSCLC, and poor PS. 3. More work is needed to understand patient perception about clinical trials. [Table: see text]

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