Stage IIIA Non-small Cell Lung Research Articles

P20.02 To Evaluate the Efficacy and Optimal Timing of Postoperative Radiotherapy in Completely Resected stage IIIA(N2) Non-Small Cell Lung Cancer

Completely resected non-small cell lung cancer (NSCLC) patients with histologically confirmed N2 disease are a heterogeneous population, with a 5-year overall survival (OS) in the range of 10-30%. After postoperative chemotherapy (POCT), 20%-40% of cases have a risk of locoregional recurrence (LRR). Due to a high degree of heterogeneity among IIIA(N2) disease, the value and optimal timing of postoperative radiotherapy (PORT) for completely resected stage IIIA(N2) NSCLC remains controversial. In this randomized clinical trial (RCT), we aimed to investigate the clinical efficacy of PORT for patients with low risk of LRR and investigate the optimal timing of PORT for those with high risk of LRR.

P01.18 Adjuvant Chemotherapy With Modified Nab-Paclitaxel and Carboplatin for Completely Resected NSCLC: Survival Analysis of FAST-Nab.

The relatively low toxicity profile of nab-paclitaxel plus carboplatin and its feasibility as an adjuvant administration was reported previously. This study aimed to evaluate the survival efficacy for completely resected patients with stage IB, II, and IIIA non-small cell lung cancer (NSCLC). Twenty-nine eligible patients with NSCLC who received surgical resection for pathological stage IB, II, or IIIA, followed by postoperative adjuvant chemotherapy with modified 3-week cycles of either nab-paclitaxel (nab-P) (100 mg/m2) on days 1 and 8 followed by carboplatin area (area under the curve=6) on day 1 were prospectively enrolled and assessed for survival outcomes against patients with the same stages who received other postoperative adjuvant chemotherapy regimens during the same period. There were no significant differences in clinicopathological features, including age, gender, smoking status, performance status, surgical procedures, tumor histology, and pathological stage between the two groups. The cumulative overall survival (OS) rates at 5 years of the experimental and control groups in pathological stage IB–IIIA were 85.4% and 63.9%, respectively (P=0.598), while recurrence-free survival (RFS) rates in these groups at 5 years were 65.2% and 34.8%, respectively (P=0.344). Moreover, the cumulative OS rates of the experimental and control groups in pathological stage II–IIIA were 83.6% and 63.6%, respectively (P=0.970), while RFS rates in these groups at 5 years were 61.1% and 37.3%, respectively (P=0.460). This new regimen was considered an attractive alternative postoperative adjuvant chemotherapy option with relatively low toxicity and moderate survival outcomes for completely resected NSCLC.

Uniportal video-assisted thoracoscopic surgery lobectomy with systematic nodal dissection for the treatment of stage IIIA (N2) non-small cell lung cancer: a case report

Uniportal video-assisted thoracoscopic surgery lobectomy with systematic nodal dissection for the treatment of stage IIIA (N2) non-small cell lung cancer: a case report

SAKK 16/14: Durvalumab in Addition to Neoadjuvant Chemotherapy in Patients With Stage IIIA(N2) Non-Small Cell Lung Cancer — A Multicentre Single-Arm Phase II Trial

SAKK 16/14: Durvalumab in Addition to Neoadjuvant Chemotherapy in Patients With Stage IIIA(N2) Non-Small Cell Lung Cancer — A Multicentre Single-Arm Phase II Trial

Neoadjuvant Treatment for Resectable, Stage IIIA Non-Small Cell Lung Cancer

Neoadjuvant Treatment for Resectable, Stage IIIA Non-Small Cell Lung Cancer

Clinical impact of the tumor immune microenvironment in completely resected stage IIIA(N2) non-small cell lung cancer based on an immunoscore approach.

Background:Completely resected stage IIIA(N2) non-small cell lung cancer (NSCLC) comprises a heterogeneous population according to discrepancies in survival prognosis. Accumulating evidence suggests that tumor-infiltrating lymphocytes (TILs) are clinically significant, despite a lack of consensus regarding the immunoscore (IS) in NSCLC. Here, we determined the prognostic value of the immune microenvironment as an IS in a uniform cohort of patients with completely resected stage IIIA(N2) NSCLC.Methods:Consecutive patients with pathologically confirmed stage IIIA(N2) NSCLC and who underwent complete resection (2005–2012) were retrospectively reviewed. Tissue microarrays (TMAs) were constructed from surgical paraffin-embedded primary lung tumor specimen. For each case, two representative regions from the tumor center (CT) and two from the invasive margin (IM) containing the highest density of lymphocytes were selected. Densities of CD3+, CD45RO+, and CD8+ lymphocytes were assessed using immunohistochemistry (IHC) by specialized pathologists according to predefined scoring scales. Patients were classified according to IS definition based on TIL type, density, and distribution, and relationships between IS and prognosis were evaluated.Results:Patients (N = 288) with complete IHC-based TMA spots were included. Univariate analyses showed that CD3+ T cell density was associated with neither overall survival (OS) nor distant metastasis-free survival (DMFS), whereas CD45RO+ T cell density in the IM was a significant prognostic factor for DMFS (p = 0.02) and was predictive of OS (p = 0.05). Combined CD45RO+ and CD8+ cell infiltration in tumor regions (CT and IM) significantly improved IS prognostic impact. Multivariate analyses revealed IS as an independent prognostic predictor for both DMFS (p = 0.001) and OS (p = 0.002).Conclusion:The proposed IS might provide valuable prognostic information, including prediction of DMFS and OS in stage IIIA(N2) NSCLC patients. Larger patient cohorts are needed to validate this IS classification, which might assist with accurate risk stratification and treatment decisions.

Comprehensive Characterization of Stage IIIA Non-Small Cell Lung Carcinoma.

IntroductionHeterogeneity of non-small cell lung carcinoma (NSCLC) among patients is currently not well studied. Pathologic markers and staging systems have not been a precise predictor of the prognosis of an individual patient. Hence, we hypothesize to develop a transcript-based signature to categorize stage IIIA-NSCLC in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), plus identify markers that could indicate the prognosis of the disease.MethodsHuman Transcriptome Array 2.0 (HTA) and NanoString nCounter® platform were used for high-throughput gene-expression profiling. Initially, we profiled stage IIIA-NSCLC through HTA and validated through NanoString. Additionally, two metastatic markers SPP1 and CDH2 were validated in 47 NSCLC stage IIIA samples through real-time PCR.ResultsWe observed distinct gene clusters in LUAD and LUSC with down-regulation of six genes and up-regulation of 57 genes through HTA. Ninety-six transcripts were randomly selected after analyzing HTA data and validated on the NanoString platform. We found 40 differentially expressed transcripts that categorized NSCLC into LUAD and LUSC. SPP1 is significantly overexpressed (4.311±1.27 fold in LUAD and 13.41±3.82 fold in LUSC compared to control), and the CDH2 transcript was significantly overexpressed (11.53 ± 4.027-fold compared to control) only in LUSC.DiscussionThese markers enable us to categorize stage IIIA NSCLC into LUAD and LUSC plus these markers may be helpful to understand the pathophysiology of NSCLC. However, more data required to make these findings useful in general clinical practice.

Surgical Management of Stage IIIA Non-small Cell Lung Cancer

There remains equipoise regarding the optimal treatment approach for patients with stage IIIA non-small cell lung cancer (NSCLC). The purpose of this review is to examine the role of surgery as a modality in the management of stage IIIA NSCLC. Over the last two decades, several studies including randomized controlled trials have established the importance of multimodality therapies in the management of locally advanced NSCLC. Significant disparities exist in the reported advantages of surgery between observational and randomized controlled studies of stage IIIA patients. While some of these differences are likely due to patient selection bias, differences in the study design and treatment-related factors may also contribute to these trends. Preliminary results from studies assessing molecular therapies and immunotherapies in this population indicate a favorable adverse event and clinical response profile. As the therapeutic armamentarium for stage IIIA disease expands, continued evaluation of surgery within multimodality treatment protocols will be increasingly important.

Adjuvant Chemotherapy Improves Survival in pN-positive Clinical Stage IIIA Non-Small Cell Lung Cancer After Neoadjuvant Therapy and Resection

The utility of adjuvant chemotherapy (AC) after neoadjuvant therapy and curative intent surgery for clinical stage IIIA (cIIIA) non-small cell lung cancer (NSCLC) is not defined. We sought to evaluate the contribution of AC to overall survival (OS) in patients with cIIIA NSCLC who underwent neoadjuvant therapy followed by curative intent surgical resection. The National Cancer Database was queried from 2010 to 2016 for patients with cIIIA NSCLC who underwent curative intent surgical resection after neoadjuvant therapy. Patients were grouped by receipt of AC, and OS was calculated using the Kaplan-Meier method. The association between mortality and AC was evaluated using Cox regression. Ninety-day landmark and propensity score-matched analyses were performed to address bias associated with early postoperative morbidity and mortality. Of 3847 patients who met the inclusion criteria, 780 received AC (20.2%). In the unadjusted cohort there was no difference in 5-year OS between the AC and no AC groups (42.8% vs 43.9%, P= .105). Cox regression demonstrated a decreased risk of mortality in pN > 0 patients receiving AC (hazard ratio, 0.79; 95% confidence interval, 0.68-0.92; P < .003), whereas no difference was seen in node-negative patients (hazard ratio, 0.95; 95% confidence interval, 0.78-1.17; P= .64). In the propensity score-matched groups OS was significantly increased in pN > 0 patients who received AC (5-year OS: 42.4% vs 37%, P < .01), whereas no survival benefit was seen in those who were pN0. For patients with completely resected cIIIA NSCLC after neoadjuvant therapy, AC is associated with an increase in OS for patients with residual pathologic lymph node involvement.

Differential expression profiling of transcripts of IDH1, CEA, Cyfra21-1, and TPA in stage IIIa non-small cell lung cancer (NSCLC) of smokers and non-smokers cases with air quality index

Smoking tobacco is the major hazard for lung cancer in Indian subcontinent especially men, compare to woman where, other important risk factors such as air pollutions are responsible. So, the aim of the study is to compare chronic smokers (CS) and non-smokers living in areas with air quality categorized as poor (AQI 201–300) or moderate (AQI 101–200). We measured the expression of non-small cell lung cancer (NSCLC) biomarkers;. IDH1, CEA, Cyfra21-1, and TPA through quantitative Real-Time PCR (qRT-PCR) and compared the levels of upregulation of the transcripts in stage IIIa NSCLC over control benign tissues among the smoking and AQI settings. Though the all biomarkers were significantly up-regulated in tumor tissues compared to control benign tissues, the fold change increase of IDH1 and CEA was highest in CS-poor/moderate AQI, followed by non-smokers-poor AQI and non-smokers moderate AQI. This indicates the aggressiveness and poor prognosis in CS living in either poor or moderate AQI areas. The level of Cyfra21-1 was lower in in the CS groups in comparison to non-smokers in the poor AQI area. This suggest higher Lung Squamous cell carcinoma histology in non-smokers living areas with poor AQI. Hence, we conclude that poor air quality can be as injurious for lung cancers as chronic smoking.

1237MO SAKK 16/14: Anti-PD-L1 antibody durvalumab in addition to neoadjuvant chemotherapy in patients with stage IIIA (N2) non-small cell lung cancer (NSCLC) – A multicenter single-arm phase II trial

1237MO SAKK 16/14: Anti-PD-L1 antibody durvalumab in addition to neoadjuvant chemotherapy in patients with stage IIIA (N2) non-small cell lung cancer (NSCLC) – A multicenter single-arm phase II trial

Determination of prognostic factors of surgically treated pathological Stage IIIA non-small cell lung cancer.

This study aims to identify the prognostic factors in Stage IIIA non-small cell lung cancer and to investigate whether there was a significant difference in terms of overall survival and diseasefree survival among the subgroups belonging to this disease stage. Between January 2010 and December 2018, a total of 144 patients (125 males, 19 females; median age 60 years; range, 41 to 80 years) who were operated for non-small cell lung cancer in our clinic and whose pathological stage was reported as IIIA were retrospectively analyzed. Data including demographic and clinical characteristics of the patients, histopathological diagnosis, the standardized uptake value of the mass on positron emission tomography-computed tomography, tumor diameter, type of surgery, lymph node metastasis status, visceral pleural invasion, and overall and disease-free survival rates were recorded. The median survival was 39 (range, 27.8 to 46.1) months and the five-year overall survival rate was 28%. The mean tumor diameter was 4.3±2.7 cm. The median disease-free survival was 37 (range, 28.1 to 48.6) months and the five-year disease-free survival rate was 26.9%. In the multivariate analysis, overall survival and disease-free survival in T2N2M0 subgroup were significantly worse than the other subgroups. The other poor prognostic factors of survival were the standardized uptake value of the tumor, pneumonectomy, and histopathological subtypes other than squamous cell carcinoma and adenocarcinoma. Parietal pleural invasion was significantly associated with worse disease-free survival rates. Our results showed that there may be significant survival differences between subgroups created by tumor histopathology, lymph node invasion and the type of surgery in a heterogeneous lung cancer stage.

Pre-treatment CT imaging in stage IIIA lung cancer: Can we predict local recurrence after definitive chemoradiotherapy?

ObjectivesThe aim of this study was to delineate computed tomography (CT) features of stage IIIA non-small cell lung cancers on pre-treatment staging studies and identify features that could predict local recurrence after definitive concurrent chemoradiotherapy. Materials and methodsWe retrospectively reviewed pre- and post-treatment CT scans for 91 patients with Stage IIIA non-small cell lung cancer undergoing definitive concurrent chemoradiotherapy. Pre-treatment CT qualitative features were evaluated by consensus. The primary endpoint was local recurrence as determined on post-treatment CT scans along with the radiotherapy fields. Local recurrence was defined as intrathoracic in-field and marginal as opposed to out-of-field failures. Competing risk regressions were used to examine associations between CT features and recurrence. ResultsThe median follow-up was 51.5 months (range 2.4–111.2). Median overall survival was 25.6 months (95% CI: 20.4–30). At last follow-up, 72 (79.1%) patients had died, 48 (52.7%) had in-field recurrence, and 30 (32.9%) presented with out-of-field recurrence. On pre-treatment CT scans, tumors presenting as pulmonary consolidations (hazard ratio = 2.34, 95% CI: 1.05–5.22; p 0.038) were more likely to have in-field failure. Tumors with 50–100% necrosis (hazard ratio = 0.15, 95% CI: 0.02–1.06) were associated with decreased out-of-field failure (overall p = 0.038). However, these were rare features in our sample which limit the ability of these features to be associated with such outcomes. ConclusionsPre-treatment CT features alone are limited in predicting locoregional recurrence. Larger studies using quantitative tools are needed to predict such outcomes.

A long-term survival case following salvage stereotactic radiotherapy for local recurrence after definitive chemoradiotherapy for stage III non-small cell lung cancer

A 56-year-old male with stage IIIA (UICC 7th) non-small cell lung cancer (adenocarcinoma) received radiotherapy with 66Gy/33 fractions concomitant with CBDCA and PTX. A partial response was achieved after chemoradiotherapy and the tumor continued to shrink over a period of 1year; however, regrowth of the tumor attached to the aortic arch was observed without any other residual tumor or metastases. We diagnosed recurrence with slightly increased18F-FDGuptake (maximum standardized uptake value: 12.2). Stereotactic radiotherapy was performed for the relapsed lesion with 60Gy/10 fractions. The patient has survived for more than 5years after stereotactic radiotherapy without recurrence or metastases, although he has been suffering from chest pain that has required treatment with a low dose of oxycodone.

Effects of Postoperative Radiotherapy on Survival of Patients With Stage IIIA Resected Non-Small Cell Lung Cancer: Analysis of the SEER Database.

The role of postoperative radiotherapy (PORT) in patients with resected stage IIIA non-small cell lung cancer (NSCLC) remains controversial. The purpose of this study was to explore the effect of PORT on survival of these patients. Patients aged ≥18 years with stage IIIA NSCLC were identified in the SEER database from 2010 through 2015. Cox regression analysis was used to identify independant prognostic factors in patients with stage IIIA NSCLC. Subgroup analysis of patients stratified by N stage was also performed. Overall survival and lung cancer-related death were compared among the different groups by using Kaplan-Meier analysis and competitive risk analysis. A total of 5,168 patients (1,711 of whom received PORT) were included in the study. In multivariable analysis, PORT was an independent prognostic risk factor for patients with N1 stage (hazard ratio [HR], 1.416, 95% CI, 1.144-1.753; P=.001). PORT was a favorable prognostic factor for patients with stage IIIA, N2 disease with ≥6 positive lymph nodes (HR, 0.742; 95% CI, 0.587-0.938; P=.012). Median survival time of patients with stage IIIA, N2 disease with ≥6 positive lymph nodes who received postoperative chemotherapy combined with PORT was significantly longer compared with those who received postoperative chemotherapy alone (32 vs 25 months, respectively; P=.009). The competitive risk model revealed that 3- and 5-year lung cancer-related mortality rates increased by 8.99% and 16.92%, respectively, in patients with N1 disease who were treated with PORT, whereas the 3-year mortality rate decreased by 4.67% and the 5-year mortality rate by 10.08% in patients with N2 disease and ≥6 positive lymph nodes who were treated using PORT. Our results revealed that PORT significantly improved overall survival and decreased lung cancer-related mortality in patients with stage IIIA, N2 disease with ≥6 positive lymph node metastases. PORT was not recommended for patients with N0 and N1 disease.

A phase I safety and feasibility study of neoadjuvant chemoradiation plus pembrolizumab followed by consolidation pembrolizumab in resectable stage IIIA non-small cell lung cancer.

9009 Background: Patients (pts) with resectable stage IIIA non-small cell lung cancer (NSCLC) have high rates of recurrence despite concurrent chemoradiation (CRT) followed by surgery. Immune checkpoint inhibitor consolidation has improved outcomes in unresectable stage III pts. Here we report the addition of concurrent neoadjuvant pembrolizumab (P) to CRT in stage IIIA patients to determine the safety and feasibility of this approach. Methods: Pts with stage IIIA NSCLC deemed resectable by a thoracic surgeon received neoadjuvant CRT consisting of cisplatin, etoposide, and concurrent P (200mg every 3 weeks x 3) with 45 Gy in 25 fractions. Pts without progression underwent resection followed by 6 months of consolidation P. The primary objective was feasibility and safety (defined as ≤30% grade 3 or higher pulmonary toxicity or any grade 4/5 nonhematologic toxicity). Ten pts were to be enrolled in Part 1, and if 2 or fewer pts had events then an additional 10 pts were to be enrolled. Secondary objectives were progression free survival (PFS), overall response rate (ORR), and pathologic complete response rate (pCR). Results: The median age of 9 enrolled pts was 66 years (range 49-76). 67% were female. 8 pts were assessable for radiographic response with an ORR of 75%. One pt came off study for progression prior to surgery and one had pleural metastases found during surgery so resection was aborted. Six pts underwent complete resection with a pCR rate of 67% (4/6). Consolidation P was started on 4 pts, with 3 completing treatment and 1 declined further treatment after 3 cycles. Median follow-up is 19.6 months and median PFS has not been reached. None of the patients who underwent resection have recurred. Serious adverse events were reported in all 9 pts with most significant being 2 grade 5 events: 1 due to pneumocystis pneumonia after resection but prior to consolidation, and 1 due to cardiac arrest during the neoadjuvant phase. Grade 3 events included 1 episode each of pneumonitis, bronchopleural fistula, acute kidney injury, colon perforation, and febrile neutropenia. Conclusions: The addition of P to neoadjuvant CRT in resectable stage IIIA pts resulted in a high pCR rate at resection. Although the relationship between grade 5 events and the addition of P was not clear, the stopping rule for infeasibility was met. As other larger studies are underway, the trial was halted rather than amended. This investigator initiated trial was funded by Merck. Clinical trial information: NCT02987998.

SAKK 16/14: Anti-PD-L1 antibody durvalumab in addition to neoadjuvant chemotherapy in patients with stage IIIA(N2) non-small cell lung cancer (NSCLC)—A multicenter single-arm phase II trial.

9016 Background: For patients (pts) with resectable stage IIIA(N2) non-small cell lung cancer (NSCLC) neoadjuvant chemotherapy (chemo) with 3 cycles cisplatin (cis)/docetaxel (doc) followed by surgery is an accepted standard of care leading to a 1-year (yr) event-free survival (EFS) of 48% and a 5-yr overall survival (OS) of 37%. PD-1/PD-L1 inhibitors have recently shown to lead to high response rates in resectable NSCLC. Methods: SAKK 16/14 is an open-label single-arm phase II study including 68 pts with resectable NSCLC stage IIIA(N2) (T1-3 N2 M0), irrespective of histological subtype, genomic aberrations or PD-L1 expression status. Neoadjuvant treatment consisted of 3 cycles of cis 100 mg/m2 and doc 85 mg/m2 q3w followed by 2 cycles of durvalumab 750 mg q2w. Durvalumab was continued after surgery q2w for 1 yr. The primary endpoint is EFS at 1 yr. The statistical hypothesis is to improve EFS at 1 yr from 48% based on the SAKK 16/00 study to 65%. Here, we report the primary endpoint and response data from 67 evaluable pts included in the study. Results: 68 pts were included from 06/16 to 01/19 and 67 pts (35 males, 32 females) were evaluable. Median age was 61 yrs (range, 41-74). 52 pts (77.6%) had a WHO PS of 0. 95.5% were current or former smokers. The majority of tumors were adenocarcinoma (55.2%) followed by squamous cell histology (32.8%). Clinical stage T1, T2 and T3 were present at diagnosis in 22.4%, 49.3% and 28.4%, respectively. 81.1% of pts underwent resection. The main reason for not undergoing surgery was disease progression (33.3%). Pneumonectomy was performed in 5 pts (9.1%), 43 pts underwent lobectomy and 7 pts bilobectomy. 30-day postoperative mortality was observed in one patient (1.8%). One patient died due to a bleeding complication after surgery most likely not related to neoadjuvant therapy. Radiographic response was 44.8% (95%CI: 32.6-57.4) after neoadjuvant chemo and 59.7% (95%CI: 46.4-71.9) after additional neoadjuvant immunotherapy. 1-yr EFS was 73.3% (90%CI: 62.5-81.4). Results for pathologic remission rate as well as correlation with PD-L1 status will be presented during the meeting. Conclusions: We report on treatment outcomes of the largest cohort of pts with resectable stage IIIA(N2) NSCLC receiving perioperative immune checkpoint inhibitor therapy. The addition of perioperative durvalumab to standard of care cis/doc is safe and leads to a high response rate and a very encouraging 1-yr EFS rate that appears substantially higher than with chemo alone. Clinical trial information: NCT 02572843.

Peripheral blood T-cell receptor immune repertoire characterization of resectable stage IIIA non-small cell lung cancer patients receiving neo-adjuvant chemo-immunotherapy treatment from NADIM study.

9041 Background: Characterization of the peripheral blood T-cell receptor (TCR) repertoire has become a novel approach to predict the clinical benefit to anti-PD1/PDL1 therapy. However, there is lack of knowledge about the clinical relevance of TCR repertoire in terms of pathological response and clinical outcomes (PFS and OS) in chemo-immunotherapy. To answer this question we have analysed samples from the NADIM study (NCT03081689), in which resectable stage IIIA NSCLC patients were treated with neoadjuvant chemo-immunotherapy with Nivolumab. Methods: Using ION Torrent-based next-generation sequencing we have analysed TCR repertoire of peripheral blood from 30 patients receiving chemo-immunotherapy. Using 25ng of total RNA from PBMCs, clonal convergence, evenness and diversity were calculated at diagnosis (pre-treatment) and after 3 cycles of Nivolumab plus carboplatin (post-treatment). Regarding pathological responses, patients were classified in 3 groups: complete response (pCR) (0% viable tumour at the resection specimen), mayor response (pMR) ( &lt; 10% viable tumour) and incomplete response (pIR) ( &gt; 10% of viable tumour). At data analysis, PFS and OS median follow-up times were longer than 20 months. Results: No statistically significant differences in TCR repertoire in terms of evenness (p = 0,373), diversity (p = 0,691) or convergence (p = 0,054) between pre- and post-neoadjuvant treatment were observed. Similarly, no significant differences were observed in these metrics between pathological response groups. However, a detailed analysis of the clones showed that the percentage of frequent clones (greater than 0.1%) that increase after neoadjuvant therapy does show differences between the different pathological response groups (pIR vs pMR), being elevated in patients who presented responses greater than 90% (p = 0.0385). Regarding the clinical benefit, having this parameter higher than the median (43,90% in this cohort) is associated with a higher PFS (p = 0.0490) and OS (p = 0.078) using KM Log-rank test. Conclusions: Evenness, Diversity and Convergence derived from immune repertoire analysis do not appear to be clinically useful in the context of neoadjuvant chemo-immunotherapy in lung cancer. However, the detailed analysis of the clones seems promising. The increase of the most frequent clones after treatment seems to be associated to different clinical variables such as pathological response and PFS in these patients. Clinical trial information: NCT03081689.

Results of neoadjuvant chemo(radio)therapy and resection for stage IIIA non-small cell lung cancer in The Netherlands

Introduction: Concurrent chemoradiotherapy remains the main treatment strategy for patients with stage IIIA non-small cell lung cancer (NSCLC); stage cT3N1 or cT4N0-1 may be eligible for surgery and potentially resectable stage IIIA (N2) NSCLC for neoadjuvant therapy followed by resection. We evaluated treatment patterns and outcomes of patients with stage IIIA NSCLC in The Netherlands.Material and Methods: Primary treatment data of patients with clinically staged IIIA NSCLC between 2010 and 2016 were extracted from The Netherlands Cancer Registry. Patient characteristics were tabulated and 5-year overall survival (OS) was calculated and reported.Results: In total, 9,591 patients were diagnosed with stage IIIA NSCLC. Of these patients, 41.3% were treated with chemoradiotherapy, 11.6% by upfront surgery and 428 patients (4.5%) received neoadjuvant treatment followed by resection. The 5-year OS was 26% after chemoradiotherapy, 40% after upfront surgery and 54% after neoadjuvant treatment followed by resection. Clinical over staging was seen in 42.3% of the patients that were operated without neoadjuvant therapy.Conclusion: In The Netherlands, between 2010 and 2016, 4.5% of patients with stage IIIA NSCLC were selected for treatment with neoadjuvant therapy followed by resection. The 5-year OS in these patients exceeded 50%. However, the outcome might be overestimated due to clinical over staging.

Risk factors of brain metastases as initial failure in completely resected stage IIIA(N2) non-small cell lung cancer.

BackgroundThis study aimed to identify the risk factors of brain metastases (BM) as the initial site of failure in patients with completely resected stage IIIA (N2) non-small-cell lung cancer (NSCLC).MethodsFrom January 2005 and June 2012, the clinical data of 357 patients with completely resected stage IIIA (N2) NSCLC were reviewed in this study. Kaplan-Meier analysis was used to identify the incidence of BM as the initial site of failure and survival. To assess the risk factors of BM, the log-rank test and Cox regression were used for univariate analysis and multivariate analysis, separately.ResultSeventy-three (20.4%) patients developed BM; 60 patients had BM as their initial site of failure. The 1-, 3-, and 5-year risk for patients developing BM as the initial site of failure was 9.1%, 27.4% and 35.4%, respectively. Univariate analysis showed adenocarcinoma histology (P=0.000), number of regional LN >4 (P=0.018), multiple N2 stations (P=0.027), multiple region of LN involvement (P=0.010) were significantly associated with an increased risk of developing BM as the initial site of failure. Multivariate analysis showed adenocarcinoma (P=0.001; HR =0.150; 95% CI, 0.047–0.479), multiple regions of LN involvement (P=0.015; HR =2.010; 95% CI, 1.146–3.524) were significantly associated with the high risk of developing BM as the initial site of failure. In patients with adenocarcinoma and multiple regions of LN involvement, the 5-year actuarial risk of BM as the initial failure was 47.6%, respectively.ConclusionsAdenocarcinoma and multiple regions of LN involvement were independent risk factors for BM as the initial failure in completely resected stage IIIA (N2) NSCLC. Prospective clinical trials are needed to verify the effect of PCI in the highest-risk subset we identified.