Large Non-small Cell Lung Cancer Research Articles

Population-Based Analysis of Local Therapies for Large (>7 cm) Non-Small Cell Lung Cancer Tumors.

This study evaluated the impact of local treatment modalities in the management of large non-small cell lung cancer (NSCLC) tumors using a nationwide population-based dataset. Patients with NSCLC tumors >7 cm that were cN0-1M0 in the Surveillance, Epidemiology, and End Results (SEER) registry from 2010 to 2015 were stratified by local management strategy (surgery, radiation therapy, no local treatment) and evaluated using Kaplan-Meier survival analyses, Cox proportional-hazard methods, and propensity-matched analysis. A total of 3156 patients were identified, of which 1580 (50.1%) underwent surgical resection, 920 (29.2%) received radiation only, 655 (20.7%) received no local treatment. Overall, the 5-year survival of patients undergoing surgical resection was 40.7%, compared to 14.7% and 5.3% for the radiation only and no local treatment groups, respectively (P < .001). Surgery with or without radiation continued to have an independent association with improved survival in multivariable analysis (HR 0.23, P < .0001). Other factors associated with improved survival included younger age, negative nodal disease, and chemotherapy use. In propensity-matched sub-analyses, 5-year survival remained significantly better after surgery alone compared to radiation alone (38.5% vs. 13.6%, P < .001), while survival after radiation alone was better than no local treatment, though both were largely poor (12.4% vs. 7.5%, P < .001). Survival of patients with large NSCLC managed non-surgically is very poor. Despite the significant long-term survival benefit with surgical intervention, nearly half of the study cohort did not undergo surgery. Patients and clinicians can use these results to estimate specific potential benefits when considering possible treatment strategies for large NSCLC tumors.

Synchronous Microwave Ablation Combined With Cisplatin Intratumoral Chemotherapy for Large Non-Small Cell Lung Cancer.

BackgroundMicrowave ablation (MWA) and intratumoral chemotherapy (ITC) are useful for treating tumors in animal models; however, their clinical use in patients with large non−small cell lung cancer (NSCLC) remains unknown. This retrospective study aimed to evaluate preliminary outcomes of MWA + ITC for large NSCLC.MethodsFrom November 2015 to April 2020, a total of 44 NSCLC patients with a mean lesion diameter of 6.1 ± 1.5 cm were enrolled and underwent synchronous MWA + ITC procedures. The primary endpoint was local progression-free survival (LPFS); secondary endpoints were progression-free survival (PFS), complications, overall survival (OS), and associated prognostic factors.ResultsThe median follow-up time was 19.0 months. At the 1-month CT scan, complete tumor ablation was observed in 47.7% of cases. Median LPFS was 12.1 months; 1-, 2-, and 3-year LPFS rates were 51.2%, 27.9%, and 13.6%, respectively. A shorter LPFS was significantly associated with large lesions (HR 1.23, 95% CI 1.02–1.49; p = 0.032). Median PFS was 8.1 months; 1-, 2-, and 3-year PFS rates were 29.5%, 18.2%, and 9.1%, respectively. LPFS was significantly superior to PFS (p = 0.046). Median OS was 18.8 months. The 1-, 2-, 3-, and 5-year OS rates were 65.9%, 43.2%, 26.4%, and 10.0%, respectively. In univariate comparisons, high performance status (PS) score, smoking, and larger lesions were significantly correlated with poor survival. In multivariate analysis, advanced age, higher PS score, higher stage, larger lesion, and prior systematic treatment were independent prognostic factors for shorter OS. Adverse events were well tolerated and all patients recovered after appropriate intervention.ConclusionsMWA + ITC is a safe and effective new modality of local treatment for large NSCLC and can significantly prolong LPFS.

GRECO-1: Phase 1/2 Study of Stereotactic Body Radiation Therapy (SBRT) With or Without GC4711 for Early Stage, Centrally Located or Large Non-Small Cell Lung Cancer (NSCLC)

<h3>Purpose/Objective(s)</h3> The number of patients diagnosed with early-stage NSCLC has been increasing with screening programs and more frequent thoracic imaging. Many patients are not ideal surgical candidates and SBRT offers an effective alternative. SBRT for larger and/or centrally located tumors is described with higher risk of toxicity and poorer local control (Timmerman 2006). Improving the safety and efficacy of SBRT with GC4711 may be of significant value in today's NSCLC management for all patients. GC4711 converts superoxide to hydrogen peroxide and has the potential to act as a radiation response modifier, increasing both tumor control and safety of SBRT. In preclinical models, the addition of selective dismutase mimetics to SBRT regimens enhanced tumor control while also protecting normal tissues from radiation damage (Sishc, AACR 2018). Consistent with this, GC4711 augmented the anti-tumor activity of SBRT in NSCLC xenograft mouse models. <h3>Materials/Methods</h3> This Phase 1/2 trial is designed to test the safety of GC4711 and its potential to reduce lung injury due to SBRT and improve tumor control for early stage cT1c-3N0M0 peripheral or centrally located (within 2cm of the proximal bronchial tree) NSCLC. An open-label, Phase 1 cohort of 5 subjects receiving GC4711, 100 mg IV (15 min), prior to each of 5 consecutive daily (M-F) SBRT fractions of 10-12Gy (Bezjak 2019) will be followed by a placebo-controlled, double-blind Phase 2 cohort of approximately 66 subjects randomized to either GC4711 or placebo concurrent with SBRT. For the primary endpoint, decline in diffusion capacity of carbon monoxide at 6 months will be compared to baseline (Stone 2015). All subjects will be followed for 12 months to report clinical (CTCAE 5.0) and radiographic pneumonitis, measured at the same time-points as quarterly lung function tests, other adverse effects, tumor control (RECIST 1.1), survival and quality of life (FACT-L). Exploratory correlative studies include ctDNA and immune profiling. <h3>Results</h3> Trial-in-progress NCT04476797 <h3>Conclusion</h3> GC4711 may improve the benefit-risk ratio of 5-fraction SBRT in early-stage NSCLC; improving tumor control while reducing the risk of lung injury.

P59.03 Intratumoral Heterogeneity and Clonal Evolution in Large Non-Small Cell Lung Cancer (>7cm) Delineated by Multiregion Sequencing

P59.03 Intratumoral Heterogeneity and Clonal Evolution in Large Non-Small Cell Lung Cancer (>7cm) Delineated by Multiregion Sequencing

Genomic characterization and outcome evaluation of kinome fusions in a large non-small cell lung cancer population.

9620 Background: Lung cancer is the leading cause of cancer death worldwide. Kinase fusion represents an important type of somatic alterations which promote oncogenesis and serve as a diagnostic marker in lung cancer. This study aims to identify the landscape of kinase fusions in lung cancer and expand our understanding of druggable fusions, together providing valuable information for therapeutics decision making. Methods: We performed genomic profiling of tumor/plasma biopsies of a total of 18,839 Chinese lung cancer patients using next generation sequencing (NGS) by targeting 425 cancer-relevant genes. Patients’ clinical characteristics and treatment history were retrospectively studied. Results: A total of 1,048 patients (5.56%, 1,048/18,839) were identified with kinase fusions, including 815 adenocarcinomas (ADCs) and 34 squamous cell carcinomas (SCCs). Briefly, a total of 198 unique gene fusion events have been observed, including 37 recurrent fusions and 114 novel fusions which have previously not been documented. ADC patients with kinase fusions were relatively younger than SCC patients (median: 53 vs 61 years old, p&lt; 0.01). The most frequently observed fusion was EML4-ALK for both ADCs (50.0%) and SCCs (32.4%), followed by FGFR3-TACC3 (29.4%) in SCCs and KIF5B-RET (11.8%), CD74-ROS1 (9.2%), CCDC6-RET (3.9%) and SLC34A2-ROS1 (2.3%) in ADCs, retrospectively. A total of 14 recurrent fusions including FN1-ALK, MEMO1-ALK, CUX1-ALK, KIF13A-RET and PHF20-NTRK1 were also identified at low frequencies. Of note, EML4- or STRN- ALK fusion events mainly rearranged in the intron 19 of ALK, but the breakpoints of VCL-ALK were mostly located upstream of ALK exon 18. Meanwhile, CD74-, SLC34A2- and TPM3- ROS1 rearrangement mainly occurred in the ROS1 introns 31, 33 and 34. In addition, among patients with novel fusions, RORB- ALK and AFF2-RET may potentially function as oncogenic drivers in lung cancer and have demonstrated clinical benefit from crizotinib treatment. Conclusions: Our data have depicted a comprehensive overview of the landscape of kinase fusions in lung cancer, which helps recognize potentially druggable fusions and translate into therapeutic applications.

Usefulness of percutaneous microwave ablation for large non-small cell lung cancer: A preliminary report.

The role of microwave ablation (MWA) in patients with non-small cell lung cancer (NSCLC) remains ill-defined. This retrospective study evaluated the oncological outcomes of CT-guided MWA in patients with large NSCLC. Kaplan-Meier analysis was used to evaluate overall survival (OS) and cancer-specific survival (CSS). The log-rank test was used to compare survival between patients with an NSCLC size greater or smaller than 4 cm. The likelihood of local tumor progression (LTP) was analyzed using a multivariable regression model. A total of 53 patients with 65 tumors were analyzed. The mean tumor size was 5.0±1.8 cm. At the 1-month CT scan, complete tumor ablation was observed in 44.6% of cases. In 18.5% of cases a redo-MWA session was carried out, while in 4.6%, a third MWA was necessary to obtain complete tumor necrosis. The mean follow-up was 28.1±20.6 months with a median duration of 21.5 months. The 1-year, 2-year, 3-year and 5-year OS rates were 78.2, 48.3, 34.8 and 18.3%, respectively. The median CSS was 25 months (95% CI 15.5–34.5). The 1-year, 2-year, 3-year and 5-year CSS rates were 84.3, 53.7, 42.1 and 30.0%, respectively. OS in patients with tumor size ≥4 cm was significantly lower when compared with those having smaller tumors (P=0.03). LTP was observed in 19 patients (35.8%). Incomplete tumor ablation [odds ratio (OR) 6.57; P<0.05] and tumor size ≥4 cm (OR 0.18; P<0.05) were significant independent predictors of LTP. In conclusion, CT-guided MWA may represent a useful tool in the multimodality treatment of patients with large advanced NSCLC.

Mesenchyme to epithelial transition protein expression, gene copy number and clinical outcome in a large non-small cell lung cancer surgical cohort.

In non-small cell lung cancer (NSCLC), mesenchyme to epithelial transition (MET) protein abundance increases with disease stage and is implicated in resistance to tyrosine kinase inhibitors. To better clarify the impact of MET overexpression on tumor behavior, we investigated a large cohort of patients who underwent curative surgical resection to determine whether MET gene amplification or protein abundance was prognostic. Tissue microarrays (TMAs) were constructed using triplicate 1 mm cores of FFPE primary NSCLC specimens. TMAs underwent immunohistochemical (IHC) staining with the SP44 clone (Ventana) and cores were considered positive if >50% of tumor exhibited 2+ staining. The highest of triplicate values was used. MET gene amplification was detected using either SISH using Ventana's MET DNP probe or FISH using the D7S486/CEP 7 Abbott Probe. DNA was subjected to mutational profiling using Sequenom's LungCarta panel. Data from two institutions comprising 763 patients (516; 68%) male were generated, including 360 stage I, 226 stage II, 160 stage III and 18 resected stage IV. High MET protein expression was detected in 25% (193/763), and was significantly more common in adenocarcinomas than squamous cell carcinoma (P<0.01). MET gene copy number (GCN) correlated with high MET protein expression by IHC (P=0.01). Increased MET protein expression was associated with EGFR and KRAS mutations (P<0.01 for both). Once polysomy was excluded, true MET gene amplification was detected in only 8/763 (1%) of samples. In multivariate analysis, neither MET protein abundance nor GCN were correlated to overall patient survival. MET expression by IHC and GCN amplification was not prognostic in this large Caucasian surgical series. MET's primary role remains as a therapeutic target.

Impact of Preoperative Radiation on Survival of Patients With Node Negative, Very Large Non-small Cell Lung Cancers (T3N0) Treated With Anatomic Resection

Impact of Preoperative Radiation on Survival of Patients With Node Negative, Very Large Non-small Cell Lung Cancers (T3N0) Treated With Anatomic Resection

QS11. Tumor-Associated Inflammatory Infiltrates Correlate With Disease Recurrence in Patients With Large Non-Small Cell Lung Cancer (NSCLC) Tumors

QS11. Tumor-Associated Inflammatory Infiltrates Correlate With Disease Recurrence in Patients With Large Non-Small Cell Lung Cancer (NSCLC) Tumors