Early-stage Non-small Lung Cancer Research Articles

P05.06 Stereotactic Ablative Radiotherapy for Early Stage Non-Small Lung Cancer and Pulmonary Oligometastases in a New Zealand Population

P05.06 Stereotactic Ablative Radiotherapy for Early Stage Non-Small Lung Cancer and Pulmonary Oligometastases in a New Zealand Population

Developing Genomic Predictive Biomarkers for Survival Benefit from Adjuvant Chemotherapy in Early-Stage Lung Cancer Patients

Surgical resection only remains the standard choice for the treatment of early-stage non-small cell lung cancer (NSCLC) patients. Preliminary studies suggest that the application of adjuvant chemotherapy with surgery (ACT) is associated with a better prognosis for more severe NSCLC patients compared to those who only underwent surgical resection. However, at an individual level, not all patients may benefit from ACT. Given the well-known adverse effects and toxicity of ACT, finding the patients that are most likely to benefit from ACT is paramount. Thus, the purpose of this research is to utilize gene expression and clinical data from lung cancer patients to develop a statistical decision support algorithm to find predictive genomic biomarkers and identify subgroups of patients who benefit from ACT. Cox regression models are trained using a randomized controlled trial gene expression data from the National Cancer Institute utilizing explicit treatment interaction terms. To handle high dimensions inherent in gene expression data, a modified-covariate regularized Cox regression model with lasso penalty is applied to find the most significant interacting covariates. Then risk scores are constructed from these models and are used to stratify patients into a high risk or low risk group respective to ACT treatment. After applying the model to an independent validation genomic data set, our methods show that patients who underwent the treatment according to their risk group exhibit a slightly higher survival rate than those who do not.

Prognostic value of the advanced lung cancer inflammation index in early-stage non-small cell lung cancer patients undergoing video-assisted thoracoscopic pulmonary resection.

The aim of this study was to assess the prognostic value of the preoperative advanced lung cancer inflammation index (ALI) in early stage non-small lung cancer (NSCLC) patients who received videoassisted thoracoscopic surgery (VATS) pulmonary surgery as their only therapy. We retrospectively reviewed the medical records of patients who were diagnosed with earlystage NSCLC and received a VATS pulmonary resection from January 2014 to June 2016 in the Department of Thoracic Surgery, West China Hospital. A receiver operating characteristic (ROC) curve analysis was conducted to determine the optimal cut-off values, and patients were divided into low and high ALI groups. The Kaplan-Meier method and Cox proportional hazards model were used to evaluate potential predictors of overall survival (OS) and disease-free survival (DFS). A total of 292 patients were enrolled in our analysis. Then, 155 and 137 patients were assigned to the low ALI (ALI <50) and high (ALI >50) groups, respectively. The multivariate analyses revealed that preoperative ALI <50 was an independent prognostic factor for both OS [hazard ratio (HR) = 2.603, 95% confidence interval (95% CI): 1.128-6.006, P=0.025] and DFS (HR =2.372, 95% CI: 1.141-4.935, P=0.021), and patients with a low preoperative ALI had worse OS (P<0.001) and DFS (P<0.001) compared with those with a high preoperative ALI. A low preoperative ALI was significantly correlated with poor survival, and the ALI might serve as a promising marker of prognosis in early-stage NSCLC patients who received a VATS pulmonary resection as their only therapy.

Comparison of clinical prognosis between stereotactic body radiotherapy and surgical treatment for early-stage non-small cell lung cancer after propensity score matching

Objective To evaluate the clinical efficacy between stereotactic body radiotherapy (SBRT) and surgical treatment for stage Ⅰ-Ⅱ non-small cell lung cancer (NSCLC). Methods Clinical data of 120 patients with early-stage NSCLC who underwent SBRT or surgical treatment in Zhejiang Cancer Hospital from 2012 to 2015 were retrospectively analyzed. Propensity score matching was carried out between two groups. Sixty eligible patients were enrolled in each group. In the SBRT group, the 80% isodose line covered 95% of the planning target volume, and the 100% isodose line covered 100% of the internal gross tumor volume. The fractional dose was 5-15 Gy and the median biologically equivalent dose was 100 Gy (range: 57.6-150.0 Gy). In the operation group, 32 patients underwent video-assisted thoracoscopic lobectomy and 9 patients underwent wedge resection or segmentectomy. Results All patients successfully completed corresponding treatment and were followed up. The median follow-up was 32.3 months (range: 8.6-68.4 months). In the operation group, 3 patients died from infection within postoperative 90 d, whereas no case died in the SBRT group (P=0.079). In the SBRT group, 3 patients died of other factors besides tumor (cerebral infarction, heart disease, etc.) during follow-up. Local-regional recurrence occurred in 12 patients including 5 cases in the operation group and 7 in the SBRT group (P=0.543). In the operation group, 11 patients experienced distant metastases with a median disease-free survival (DFS) of 33.5 months. In the SBRT group, 6 patients had distant metastases and the median DFS was 38.4 months (P=0.835, P=0.178). In the SBRT group, the 1-and 3-year overall survival rates were 93% and 83%, and 95% and 83% in the operation group (P=0.993). Conclusions The 1-and 3-year overall survival rates and local control rate do not significantly differ between SBRT and operation for patients with early-stage NSCLC. Key words: Lung neoplasms/stereotactic body radiotherapy; Lung neoplasms/surgery; Treatment outcome

OA040] Quantifying the effect of increased tissue definition on inter-observer variation in contouring of organs at risk in lung cancer patients using motion-compensated imaging

Purpose The development of 4DCT imaging allows clinicians to account for movement of both the target tumour and organs at risk, although the choice of method of image reconstruction can impact how accurately observers can contour nearby organs. Motion-compensated (MC) image reconstruction is a technique that reduces blurring compared to standard averaged reconstruction. This study aims to quantify the presence of sharper boundaries by taking the value of the image gradient at contour lines, and link this increase in tissue definition to lower inter-observer variation. Methods Eight patients with early stage non-small lung cancer were imaged with 4DCT, and these scans were reconstructed using both motion-compensated and averaged techniques. These two sets of scans were then each delineated by five clinicians, who contoured nearby organs at risk. The mean distance between observers’ contours was calculated and compared to the image gradient value at each point on the delineation. Results Drawing on results by McWilliam et al. [1] , the use of motion-compensated CT image reconstruction results in a reduction in inter-observer variation across all sites delineated. The use of MC increases definition of boundaries between organs, represented by an increase in the image gradient at the delineation boundary. This result was particularly pronounced around the trachea, where preliminary results show the use of motion-compensated reconstruction reduced delineation separation by 50%; across all patients, the heart saw very little improvement between imaging techniques. Conclusions The use of motion-compensated CT reconstruction produces images with more well-defined boundaries between tissue, and higher values of image gradient. When delineating organs at risk, the presence of large gradients is a statistically significant (p

Comparative analysis of clinical efficacy between stereotactic ablative radiotherapy and surgery for early-stage non-small cell lung cancer

Objective To compare the clinical efficacy and safety between stereotactic ablative radiotherapy (SABR) and surgery in the treatment of early-stage non-small cell lung cancer (NSCLC). Methods A total of 227 patients who were initially diagnosed with early-stage NSCLC and with complete clinical data admitted to Henan Cancer Hospital between June 2012 and December 2016 were recruited and assigned into the SABR (n=73) and surgery groups (n=154). Kaplan-Meier method was used to calculate survival rate and survival comparison was performed using the log-rank test. Chi-square test was adopted to compare the baseline data between two groups. Results All patients completed corresponding treatment. The samples of SABR group and operation group were 74 and 155 cases respectively. The 1-year and 3-year overall survival (OS) rates in the SABR and surgery groups were 97.2%, 81.9% and 96.5%, 78.2%(P=0.603), respectively. The 1-year and 3-year progression-free survival (PFS) rates in the SABR and surgery groups were 90.1%, 66.9% and 89.2%, 66.9%(P=0.565), respectively. The 1-year and 3-year locoregional recurrence-free survival rates in the SABR and surgery groups were 92.8%, 84.0% and 96.5%, 90.8%(P=0.133), respectively. The 1-year and 3-year distant metastasis-free survival rates in the SABR and surgery groups were 97.2%, 75.4% and 89.2%, 69.8%(P=0.095), respectively. Conclusions SABR and surgery yield similar OS, PFS, locoregional recurrence-free and distant metastasis-free survival rates in the treatment of early-stage NSCLC. Therefore, SABR is an alternative treatment for patients with early-stage NSCLC. Key words: Carcinoma, non-small cell lung/radiotherapy; Radiotherapy, stereotactic ablative; Prognosis

ED08.01 Surgery of Early-Stage NSCLC

ED08.01 Surgery of Early-Stage NSCLC

18F-FDG PET/CT in evaluation of the outcome after stereotactic body radiation therapy for early-stage non-small cell lung cancer

Stereotactic body radiation therapy (SBRT) has been increasingly used in the treatment of early-stage NSCLC, especially for patients who cannot undergo surgery. Compared with other imaging modalities, PET/CT has higher sensitivity and specificity in diagnosis and staging of NSCLC as well as higher prediction value for prognosis. The progress of 18F-FDG PET/CT in evaluation of the therapeutic response and prognosis after SBRT for early-stage NSCLC is summarized in this review. Key words: Radiotherapy; Carcinoma, non-small-cell lung; Tomography, emission-computed; Tomography, X-ray computed; Trends

Expression of miR-29c, miR-93, and miR-429 as Potential Biomarkers for Detection of Early Stage Non-Small Lung Cancer

BackgroundAltered expression of miRNA expression contributes to human carcinogenesis. This study was designed to detect aberrant miRNA expressions as a potential biomarker for early detection and prognosis prediction of non-small cell lung cancer (NSCLC).MethodsmiRNA array was used to profile differentially expressed miRNAs and Taqman-based quantitative RT-PCR assays were used to analyze levels of miR-29c, miR-93, and miR-429 expression in NSCLC tissue samples, corresponding normal tissue samples, and serum samples from 70 NSCLC patients as well as in serum samples from 48 healthy controls.ResultsLevels of miR-29c and miR-93 expression were upregulated in NSCLC tissues, while serum levels of miR-29c were also upregulated, but levels of serum miR-429 were decreased in NSCLC. Moreover, the levels of miR-429 expression in NSCLC tissues were associated with those in serum samples. Receiver operating characteristic (ROC) curve analysis showed that at the optimal cut-off point, the areas under the ROC curve for serum levels of miR-29c and miR-429 were 0.723 and 0.727, respectively, levels which are higher than that of carcinoma embryonic antigen (0.534) in diagnosis of stage I NSCLC. In addition, serum levels of miR-429 were associated with poor overall survival of NSCLC patients. Both univariate and multivariate analyses showed that serum miR-429 level was an independent prognostic predictor for NSCLC.ConclusionsThe results of the current study suggest that detection of serum miR-29c and miR-429 expression should be further evaluated as a novel, non-invasive biomarker for early stage NSCLC.

The validation of estrogen receptor 1 mRNA expression as a predictor of outcome in patients with metastatic non-small cell lung cancer

The prognostic role of estrogen receptors in lung cancer is not validated. Results from patients with early stage non-small lung cancer patients indicate a prognostic role of estrogen receptor 1 (ESR1) mRNA expression in these patients. Automated RNA extraction from paraffin and RT-quantitative PCR was used for evaluation of tumoral ESR1 and progesterone receptor (PGR) mRNA expression. The test cohort consisted of 31 patients with advanced or metastatic non-small cell lung cancer (NSCLC) patients, treated in a first-line registry trial. For validation, 53 patients from a randomized multicentre first-line study with eligible tumor samples were evaluated. There was no significant correlation of ESR1 expression with clinical characteristics. ESR1 high expression was of significant positive prognostic value in the training set with a median overall survival (OS) of 15.9 versus 6.2 months for high versus low ESR1 expression patients (p = 0.0498, HR 0.39). This could be confirmed in the validation cohort with a median OS of 10.9 versus 5.0 months in ESR1 high versus low patients, respectively (p = 0.0321, HR 0.51). In the multivariate analysis adjusted for histological subtype, gender, age and performance status, ESR1 expression remained an independent prognostic parameter for survival in both cohorts. In contrast to ESR1, PGR expression was not able to separate prognostic groups or to predict outcome significantly (for OS; p = 0.94). Our study shows that ESR1 mRNA as assessed by qPCR represents a reliable method for detecting ESR1 expression in NSCLC and that ESR1 expression is an independent prognostic factor in metastatic NSCLC.

Analytical variables influencing the performance of a miRNA based laboratory assay for prediction of relapse in stage I non-small cell lung cancer (NSCLC)

BackgroundLaboratory assays are needed for early stage non-small lung cancer (NSCLC) that can link molecular and clinical heterogeneity to predict relapse after surgical resection. We technically validated two miRNA assays for prediction of relapse in NSCLC. Total RNA from seventy-five formalin-fixed and paraffin-embedded (FFPE) specimens was extracted, labeled and hybridized to Affymetrix miRNA arrays using different RNA input amounts, ATP-mix dilutions, array lots and RNA extraction- and labeling methods in a total of 166 hybridizations. Two combinations of RNA extraction- and labeling methods (assays I and II) were applied to a cohort of 68 early stage NSCLC patients.ResultsRNA input amount and RNA extraction- and labeling methods affected signal intensity and the number of detected probes and probe sets, and caused large variation, whereas different ATP-mix dilutions and array lots did not. Leave-one-out accuracies for prediction of relapse were 63% and 73% for the two assays. Prognosticator calls ("no recurrence" or "recurrence") were consistent, independent on RNA amount, ATP-mix dilution, array lots and RNA extraction method. The calls were not robust to changes in labeling method.ConclusionsIn this study, we demonstrate that some analytical conditions such as RNA extraction- and labeling methods are important for the variation in assay performance whereas others are not. Thus, careful optimization that address all analytical steps and variables can improve the accuracy of prediction and facilitate the introduction of microRNA arrays in the clinic for prediction of relapse in stage I non-small cell lung cancer (NSCLC).

Postoperative adjuvant therapy for completely resected early-stage non-small cell lung cancer

Postoperative adjuvant therapy for completely resected early-stage non-small cell lung cancer

Pulmonary injury and tumor response after stereotactic body radiotherapy (SBRT): Results of a serial follow-up CT study

Purpose To evaluate the CT morphological pattern of tumor response and pulmonary injury after stereotactic body radiotherapy (SBRT) for early stage non-small lung cancer (NSCLC) and pulmonary metastases. Materials and methods Seventy patients (lesions n = 86) with pulmonary metastases ( n = 48) or primary early stage NSCLC ( n = 38) were analyzed. Patients were treated with hypofractionated SBRT (three to eight fractions with a single dose between 6 and 12.5 Gy; n = 56) or with radiosurgery (26 Gy; n = 30). The pattern and sequence of pulmonary injury and of tumor response was evaluated in 346 follow-up CT studies, 4.9 on average. Results Symptomatic pneumonitis was observed in 10% after a median interval of 5 months. No pulmonary reaction was observed in most patients 6 weeks after treatment; spotted-streaky condensations were characteristic between 3 months and 6 months. Dense consolidation and retraction started after 9 months and the fibrotic remodelling process continued for years. Ten targets relapsed after a median of 7 months. At 12 months complete response was seen in 43% and the differentiation of residual tumor from pulmonary reaction was not possible in 33%. Conclusions A typical sequence of pulmonary reactions was observed without differences between hypofractionated treatment and radiosurgery. Onset of pneumonitis was later compared to conventionally fractionated radiotherapy.