Human papillomavirus (HPV)-associated early stage non-small cell lung cancer (NSCLC).

7560 Background: HPV is an established risk factor for cervical and oropharyngeal cancer. It has been suggested as a potential risk factor for lung cancer based on studies conducted mostly in Asian patients with advanced NSCLC. We characterize potential role of HPV in a North American patient population with early stage NSCLC. Methods: We analyzed surgically resected samples of NSCLC patients diagnosed between 2002-2007. HPV status was determined by polymerase chain reaction (PCR) using the INNO-LiPA genotyping Extra Amplification and Genotyping Extra kits, followed by reverse hybridization line probe assay to identify specific HPV serotypes. Differences between HPV+ and HPV- patients were assessed by Chi-square, Fisher’s exact, and Wilcoxon rank-sum tests. Survival was estimated by the Kaplan-Meier method and differences between HPV+ and HPV- patients were assessed by Log-rank test. Multivariable logistic regression modeling was employed to select predictors of HPV+ NSCLC. The significance levels were set at 0.05 for all tests. Results: Paraffin-embedded tumor samples from 208 patients were analyzed; M/F (49%/51%); stage I: 80%; II: 11%; III: 9%; IV: <1%; Caucasians 95.6% and African-Americans (AA) 4.4%. There were 32 (14.9%) HPV+ cases including 10 cases with HPV 16/18. Ethnicity was significantly associated with HPV status (p-value=0.033). AA patients are more likely to be HPV+ (OR: 7.373; p=0.01) and more likely to harbor high risk serotypes 16/18 (OR: 10.8; p=0.05). Regression modeling identified AA ethnicity, adenocarcinoma (ADC) histology and current smoking (parameter estimates of 2.04, -2.34 and -2.82 respectively) as predictors of HPV+ NSCLC. Smoking status and histology showed significant interaction in predicting HPV+ tumors: OR: 0.06; p=0.0023 for smokers with squamous cancer; 2.52; p=0.24 for smokers with ADC and 10.339; p=0.0293 for smokers with adenosquamous cancer. Median disease free survival (NR; p=0.42) and median overall survival (71 months; vs. 55 months) were not significantly different between HPV+ and HPV- patients. Conclusions: HPV positivity is observed in 15% of early stage NSCLC with strong association with AA ethnicity, adenosquamous histology and non-smoking status.

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Development of a serum miRNA panel for detection of early stage non-small cell lung cancer

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2006212117 ◽

2020 ◽

Vol 117 (40) ◽

pp. 25036-25042 ◽

Cited By ~ 2

Author(s):

Lisha Ying ◽

Lingbin Du ◽

Ruiyang Zou ◽

Lei Shi ◽

Nan Zhang ◽

...

Keyword(s):

Lung Cancer ◽

Early Detection ◽

Minimally Invasive ◽

Cell Lung Cancer ◽

Early Stage ◽

Smoking Status ◽

Nonsmall Cell Lung Cancer ◽

Improve Patient Survival ◽

Early Stage Nsclc ◽

Invasive Test

Minimally invasive testing for early detection of lung cancer to improve patient survival is a major unmet clinical need. This study aimed to develop and validate a serum multi-microRNA (multimiR) panel as a minimally invasive test for early detection of nonsmall cell lung cancer (NSCLC) regardless of smoking status, gender, and ethnicity. Our study included 744 NSCLC cases and 944 matched controls, including smokers and nonsmokers, male and female, with Asian and Caucasian subjects. Using RT-qPCR and a tightly controlled workflow, we quantified the absolute expression of 520 circulating microRNAs (miRNAs) in a Chinese cohort of 180 early stage NSCLC cases and 216 healthy controls (male smokers). Candidate biomarkers were verified in two case-control cohorts of 432 Chinese and 218 Caucasians, respectively (including females and nonsmokers). A multimiR panel for NSCLC detection was developed using a twofold cross-validation and validated in three additional Asian cohorts comprising 642 subjects. We discovered 35 candidate miRNA biomarkers, verified 22 of them, and developed a five-miR panel that detected NSCLC with area under curve (AUC) of 0.936–0.984 in the discovery and verification cohorts. The panel was validated in three independent cohorts with AUCs of 0.973, 0.916, and 0.917. The sensitivity of five-miR test was 81.3% for all stages, 82.9% for stages I and II, and 83.0% for stage I NSCLC, when the specificity is at 90.7%. We developed a minimally invasive five-miR serum test for detecting early stage NSCLC and validated its performance in multiple patient cohorts independent of smoking status, gender, and ethnicity.

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Does presence of chronic obstructive pulmonary disease (COPD) influence clinical behavior in patients with early-stage non-small cell lung cancer (ESNSCLC)?

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e18530 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e18530-e18530

Author(s):

Satomi Yamamoto ◽

Tomoya Kawaguchi ◽

Taro Tamura ◽

Kazuhiro Asami ◽

Kyoichi Okishio ◽

...

Keyword(s):

Lung Cancer ◽

Early Stage ◽

Smoking Status ◽

Performance Status ◽

Disease Free Survival ◽

Lymphatic Invasion ◽

Stage I ◽

Chronic Obstructive ◽

Wild Type ◽

Significant Difference

e18530 Background: CDPD and lung cancer sometimes occurs simultaneously. COPD has been recognized as an inflammatory disease and may potentially affect biology of the accompanying tumor. It is not fully understood whether presence of CDPD influences clinical characteristics, pathological findings and/or clinical outcomes in patients with ESNSCLC. Methods: Retrospective and consecutive data were collected from the medical records of patients who underwent surgical resections at Kinki-chuo Chest Medical Center, Japan, between January 2009 and December 2010. CDPD status was classified as absence of COPD, stage I and II COPD based on the criteria of Global Initiative for Chronic Obstructive Lung Disease (GOLD). Histology, vascular / lymphatic invasion and the status of epidermal growth factor receptor (EGFR) were determined using the surgical materials. Results: A total of 319 cases was included with median age of 67 (range, 36 - 89). There were 81 cases of relapse and 40 cases of death during the median follow up of 28 months (11 days to 49 months). In the subgroup of non-COPD, stage I and II COPD, the median age, the number of case in gender (male/female), performance status (PS, 0/1), histology (squamous cell carcinoma [SQ] /non SQ), smoking status (never/ever), and EGFR status (wild type/mutant) were 67, 72, 72 (p<0.001) and 105/110, 48/12, 38/6 (p<0.001) and 170/40, 53/7, 27/14 (p=0.029) and 31/184, 12/48, 14/28 (p<0.001) and 89/122, 7/53, 2/39 (p=0.002) and 47/37, 21/3, 9/3 (p=0.013), respectively. No significant difference was observed in disease-free survival (DFS, log-rank p=0.411) and overall survival (OS, log-rank p=0.127) between the patients with and without COPD. In multivariate analysis adjusted for age, gender, PS, histology, smoking status, pathological stage, vascular / lymphatic invasion and EGFR status, presence of COPD did not affect DFS (HR=1.457, p = 0.279) nor OS (HR=0.993, p = 0.990).Conclusions: Although COPD was significantly associated with the elderly, male gender, presence of symptoms, SQ histology, ever smoking, and wild type EGFR, it did not add values of prognostic factors in patients with ESNSCLC.

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Occult Metastases in Lymph Nodes Predict Survival in Resectable Non–Small-Cell Lung Cancer: Report of the ACOSOG Z0040 Trial

Journal of Clinical Oncology ◽

10.1200/jco.2011.35.2500 ◽

2011 ◽

Vol 29 (32) ◽

pp. 4313-4319 ◽

Cited By ~ 53

Author(s):

Valerie W. Rusch ◽

Debra Hawes ◽

Paul A. Decker ◽

Sue Ellen Martin ◽

Andrea Abati ◽

...

Keyword(s):

Lung Cancer ◽

Lymph Nodes ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Early Stage ◽

Disease Free Survival ◽

Small Cell ◽

Small Cell Lung ◽

Occult Metastases ◽

Early Stage Nsclc

Purpose The survival of patients with non–small-cell lung cancer (NSCLC), even when resectable, remains poor. Several small studies suggest that occult metastases (OMs) in pleura, bone marrow (BM), or lymph nodes (LNs) are present in early-stage NSCLC and are associated with a poor outcome. We investigated the prevalence of OMs in resectable NSCLC and their relationship with survival. Patients and Methods Eligible patients had previously untreated, potentially resectable NSCLC. Saline lavage of the pleural space, performed before and after pulmonary resection, was examined cytologically. Rib BM and all histologically negative LNs (N0) were examined for OM, diagnosed by cytokeratin immunohistochemistry (IHC). Survival probabilities were estimated using the Kaplan-Meier method. The log-rank test and Cox proportional hazards regression model were used to compare survival of groups of patients. P < .05 was considered significant. Results From July 1999 to March 2004, 1,047 eligible patients (538 men and 509 women; median age, 67.2 years) were entered onto the study, of whom 50% had adenocarcinoma and 66% had stage I NSCLC. Pleural lavage was cytologically positive in only 29 patients. OMs were identified in 66 (8.0%) of 821 BM specimens and 130 (22.4%) of 580 LN specimens. In univariate and multivariable analyses OMs in LN but not BM were associated with significantly worse disease-free survival (hazard ratio [HR], 1.50; P = .031) and overall survival (HR, 1.58; P = .009). Conclusion In early-stage NSCLC, LN OMs detected by IHC identify patients with a worse prognosis. Future clinical trials should test the role of IHC in identifying patients for adjuvant therapy.

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

Cancers ◽

10.3390/cancers13020176 ◽

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.

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

Experimental Biology and Medicine ◽

10.1177/1535370220945987 ◽

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.

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Radiomics Signature: A Potential Biomarker for the Prediction of Disease-Free Survival in Early-Stage (I or II) Non—Small Cell Lung Cancer

Radiology ◽

10.1148/radiol.2016152234 ◽

2016 ◽

Vol 281 (3) ◽

pp. 947-957 ◽

Cited By ~ 238

Author(s):

Yanqi Huang ◽

Zaiyi Liu ◽

Lan He ◽

Xin Chen ◽

Dan Pan ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Early Stage ◽

Disease Free Survival ◽

Small Cell ◽

Small Cell Lung ◽

Free Survival ◽

Potential Biomarker ◽

Disease Free ◽

Radiomics Signature

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

Journal of Clinical Oncology ◽

10.1200/jco.2008.18.7906 ◽

2009 ◽

Vol 27 (16) ◽

pp. 2660-2667 ◽

Cited By ~ 87

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.

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

10.21203/rs.3.rs-458770/v1 ◽

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.

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

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.8538 ◽

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.

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