PD1.04 Topic: Early Stage NSCLC (Stage I - III) Mid-term Outcomes of Uniportal Vats(U-VATS) for Early Lung Cancer

This review examines studies of radiofrequency ablation (RFA) of nonsmall cell lung cancer (NSCLC) and discusses the role of RFA in treatment of early-stage NSCLC. RFA is usually performed under local anesthesia with computed tomography guidance. RFA-associated mortality, while being rare, can result from pulmonary events. RFA causes pneumothorax in up to 63% of cases, although pneumothorax requiring chest drainage occurs in less than 15% of procedures. Other severe complications are rare. After RFA of stage I NSCLC, 31–42% of patients show local progression. The 1-, 2-, 3-, and 5-year overall survival rates after RFA of stage I NSCLC were 78% to 100%, 53% to 86%, 36% to 88%, and 25% to 61%, respectively. The median survival time ranged from 29 to 67 months. The 1-, 2-, and 3-year cancer-specific survival rates after RFA of stage I NSCLC were 89% to 100%, 92% to 93%, and 59% to 88%, respectively. RFA has a higher local failure rate than sublobar resection and stereotactic body radiation therapy (SBRT). Therefore, RFA may currently be reserved for early-stage NSCLC patients who are unfit for sublobar resection or SBRT. Various technologies are being developed to improve clinical outcomes of RFA for early-stage NSCLC.

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Outcome of the radical hypofractioned radiotherapy treatment in patients with stage I and II of non-small cell lung cancer

Journal of Radiotherapy in Practice ◽

10.1017/s1460396912000052 ◽

2012 ◽

Vol 12 (2) ◽

pp. 139-145

Author(s):

Maria Wilczynska ◽

Angel Garcia-Alonso

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Median Survival ◽

Cell Lung Cancer ◽

Early Stage ◽

Small Cell ◽

Stage I ◽

Radical Radiotherapy ◽

Small Cell Lung ◽

Early Stage Nsclc

AbstractIntroduction: Surgery is the treatment of choice in stage I and II non-small-cell lung cancer (NSCLC). In the management of patients who are medically unfit to tolerate surgical intervention or who refuse surgery, radiotherapy is an acceptable alternative. We have performed a retrospective analysis of the effectiveness of radical radiotherapy in patients with early stage NSCLC treated over a period of 4 years.Methods: Thirty nine patients treated with radiotherapy of radical intent were identified. All patients received hypofractionated radiotherapy with a total dose of 55Gy in 20 fractions.Results: The median survival of all cases was 29 months. The one and two-year survival was respectively 61 % and 41%. The median survival of patients ≥75 years was 28 months, and age was the only prognostic factor identified in this analysis that affected survival.Conclusions: The presented survival results are consistent with those from other series published in the literature. At present, radical radiotherapy is often offered to patients with medically inoperable stage I and II NSCLC or those who decline surgery. But there is emerging evidence that some new techniques like stereotactic radiotherapy could be also used in the operable, early stage NSCLC.

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Competing mortality (CM) risk in patients with resected stage I and II non-small cell lung cancer (NSCLC): A Surveillance, Epidemiology, and End Results (SEER) analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.7563 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 7563-7563

Author(s):

Gayathri Nagaraj ◽

Janakiraman Subramanian ◽

Feng Gao ◽

Siddhartha Devarakonda ◽

Ramaswamy Govindan

Keyword(s):

Risk Factors ◽

Lung Cancer ◽

Clinical Trials ◽

Sample Size ◽

Cumulative Incidence ◽

Early Stage ◽

Stage I ◽

Data Set ◽

Early Stage Nsclc ◽

The Impact

7563 Background: CM risk has been identified as a potential confounder in the interpretation of treatment effects in head and neck cancer (Rose et al. J Clin Oncol. 2011). Lung cancer patients (pts) are at considerable risk for CM due to their advanced age at diagnosis and smoking related chronic diseases. We plan to identify risk factors for CM in pts with early stage NSCLC and develop a statistical model to estimate the effect of CM on power calculation for lung cancer clinical trials. Methods: Using SEER registry we identified 32104 pts who had undergone surgical resection with or without radiation for stage I and II NSCLC between 1994 and 2006. The data set was split into two groups: training set (75%) and testing set (25%). Risk factors for lung cancer-specific mortality (LCSM) and CM were identified using training data by Gray’s sub-distribution regression of competing risk. Pts from the testing data were then stratified according to CM risk and the impact of this risk on power loss was evaluated. Results: The 5-year cumulative incidence of death from lung cancer, other causes and overall mortality was 32.7%, 14.2% and 46.9% respectively. Risk factors for CM were: age (hazard ratio [HR] 1.05), male gender (HR 1.43), divorced (HR 1.30), widowed (HR 1.23) or single (HR 1.29) marital status, squamous (HR 1.40) or not-otherwise-specified (HR 1.22) histology, stage I NSCLC (HR 1.27) and sublobar resection (HR 1.23). The 5-year cumulative incidence of CM in low, mid and high-risk tertiles was 7%, 14% and 21% respectively. Sample size calculations based on all-cause mortality (ACM) result in over-estimation of power as the risk for CM increases. In order to restore the underestimated power in LCSM, 19% and 35% more pts are required in the mid and high CM risk groups respectively (Table). Conclusions: Our findings indicate that conventional sample size calculation methods can result in significant loss of power and incorporating CM risk models in power estimation should be considered for clinical trials involving early stage NSCLC pts. [Table: see text]

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Detection of residual disease and recurrence in early-stage non-small cell lung cancer (NSCLC) patients using sensitive personalized ctDNA sequencing assays.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e15560 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e15560-e15560

Author(s):

Katrin Heider ◽

Davina Gillian Gale ◽

Giovanni Marsico ◽

Andrea Ruiz-Valdepeñas ◽

Garima Sharma ◽

...

Keyword(s):

Lung Cancer ◽

Residual Disease ◽

Early Stage ◽

Small Cell ◽

Post Treatment ◽

Stage I ◽

Small Cell Lung ◽

Curative Intent ◽

Early Stage Nsclc ◽

Generation Sequencing

e15560 Background: Detection of residual circulating tumour DNA (ctDNA) in patient plasma following curative intervention for localized non-small cell lung cancer (NSCLC) could identify patients who are at higher risk of relapse. These patients may benefit from adjuvant treatment, even if they have no macroscopic disease identified by radiographic imaging, which is the current standard of care. Here we evaluate the performance of the Inivata personalized sequencing assays to detect ctDNA in a cohort of 90 patients with early-stage NSCLC undergoing treatment with curative intent. Methods: The Inivata assay uses a highly sensitive next-generation sequencing platform, to identify tumor-specific variants from exome sequencing of tumor tissue and to track up to 48 patient-specific mutations in plasma specimens by multiplex PCR and ultra-high-depth next-generation sequencing. Samples from 90 patients with Stage I-III NSCLC who underwent radical treatment with curative intent, either surgery or radiotherapy ± chemotherapy, were collected as part of the LUng cancer - CIrculating tumor DNA (LUCID) study. Results: 350 plasma samples from 90 patients were analyzed using the Inivata assay, including samples collected before and after treatment and at subsequent follow-up visits. ctDNA was detected in pre-treatment samples in 38% of 32 patients (12/32) with Stage I NSCLC and in 90% of 21 patients (19/21) with Stage II/III disease, at allele fractions ranging from 6 parts per million (ppm, equivalent to 0.0006%) to over 20,000 ppm (equivalent to 2%). In plasma samples collected post-treatment, ctDNA was detected in close to 50% of cases. Conclusions: These findings highlight the Inivata assay is a sensitive method for detection of residual ctDNA and recurrence in early stage NSCLC. Initial detection rates ranged from 38% in Stage I disease to 90% for patients with Stage II/III disease prior to treatment, including detection of ctDNA to levels as low as a few parts per million. ctDNA was detected in at least one post-treatment timepoint in close to 50% patients. Together with additional data to be presented from the full 90 patient cohort, this suggests a possible route to improving treatment and designs of adjuvant trials for early stage NSCLC by detection of residual disease post-treatment and monitoring for early detection of relapse.

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Green synthesis of nanomaterials for early lung cancer detection

Journal of Cancer Science and Therapeutics ◽

10.36879/jcst.18.000102 ◽

2018 ◽

pp. 1-1

Keyword(s):

Lung Cancer ◽

Green Synthesis ◽

Cancer Detection ◽

World Wide ◽

Early Stage ◽

Age Groups ◽

Early Lung Cancer ◽

Lung Cancer Detection ◽

Synthesis Of Nanomaterials

Lung cancer is the foremost cause of cancer-related deaths world-wide [1]. It affects 100,000 Americans of the smoking population every year of all age groups, particularly those above 50 years of the smoking population [2]. In India, 51,000 lung cancer deaths were reported in 2012, which include 41,000 men and 10,000 women [3]. It is the leading cause of cancer deaths in men; however, in women, it ranked ninth among all cancerous deaths [4]. It is possible to detect the lung cancer at a very early stage, providing a much higher chance of survival for the patients.

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LOW-DOSE COMPUTED TOMOGRAPHY IN MOSCOW FOR LUNG CANCER SCREENING (LDCT-MLCS): BASELINE RESULTS

Problems in oncology ◽

10.37469/0507-3758-2019-65-2-224-233 ◽

2019 ◽

Vol 65 (2) ◽

pp. 224-233

Author(s):

Sergey Morozov ◽

Viktor Gombolevskiy ◽

Anton Vladzimirskiy ◽

Albina Laypan ◽

Pavel Kononets ◽

...

Keyword(s):

Computed Tomography ◽

Lung Cancer ◽

Cancer Screening ◽

Low Dose ◽

Early Stage ◽

Lung Cancer Screening ◽

Stage I ◽

Malignant Neoplasms ◽

Number Needed To Screen ◽

Low Dose Computed Tomography

Study aim. To justify selective lung cancer screening via low-dose computed tomography and evaluate its effectiveness. Materials and methods. In 2017 we have concluded the baseline stage of “Lowdose computed tomography in Moscow for lung cancer screening (LDCT-MLCS)” trial. The trial included 10 outpatient clinics with 64-detector CT units (Toshiba Aquilion 64 and Toshiba CLX). Special low-dose protocols have been developed for each unit with maximum effective dose of 1 mSv (in accordance with the requirements of paragraph 2.2.1, Sanitary Regulations 2.6.1.1192-03). The study involved 5,310 patients (53% men, 47% women) aged 18-92 years (mean age 62 years). Diagnosis verification was carried out in the specialized medical organizations via consultations, additional instrumental, laboratory as well as pathohistological studies. The results were then entered into the “National Cancer Registry”. Results. 5310 patients (53% men, 47% women) aged 18 to 92 years (an average of 62 years) participated in the LDCT-MLCS. The final cohort was comprised of 4762 (89.6%) patients. We have detected 291 (6.1%) Lung-RADS 3 lesions, 228 (4.8%) Lung- RADS 4A lesions and 196 (4.1%) Lung-RADS 4B/4X lesions. All 4B and 4X lesions were routed in accordance with the project's methodology and legislative documents. Malignant neoplasms were verified in 84 cases (1.76% of the cohort). Stage I-II lung cancer was actively detected in 40.3% of these individuals. For the first time in the Russian Federation we have calculated the number needed to screen (NNS) to identify one lung cancer (NNS=57) and to detect one Stage I lung cancer (NNS=207). Conclusions. Based on the global experience and our own practices, we argue that selective LDCT is the most systematic solution to the problem of early-stage lung cancer screening.

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Surgery in Small-Cell Lung Cancer

Cancers ◽

10.3390/cancers13030390 ◽

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.

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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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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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