Surgery after neoadjuvant immunochemotherapy versus immuno-chemoradiotherapy in patients with cN3 non-small cell lung cancer: A cohort study in two academic centers.

Stereotactic Body Radiation Therapy for the Treatment of Early-stage Bronchoalveolar Carcinoma: A Patterns of Failure Analysis

ED08.04 Perspectives of Targeted Therapies and Immunotherapy in Completely Resected NSCLC

Stereotactic Body Radiotherapy Versus Surgery for Patients with Stage I Non-Small-Cell Lung Cancer: Comparison of Long-Term Outcome with a Propensity Score Matching Analysis

Role of Stereotactic Body Radiotherapy for Early-Stage Non-Small Cell Lung Cancer in Borderline Patients for Surgery due to Impaired Pulmonary Function

8045 Background: Stage IIIB-IIIC (N3) non-small cell lung cancer (NSCLC) is generally seen as unresectable, and Durvalumab following concurrent chemoradiotherapy (CCRT) is the standard of care for these patients. The use of immune checkpoint inhibitor (ICI) in neoadjuvant therapy has resulted in unprecedented rates of pathological response and lymph node downstaging, which has made resecting previous unresectable disease possible. However, it remains uncertain whether certain N3 patients may derive survival benefit from surgery after neoadjuvant immunotherapy. Methods: This multicenter retrospective study included patients with cN3 NSCLC who received inducing immunochemotherapy and completed surgery. As a comparison, patients with cN3 NSCLC who received ICI following CCRT, ICI plus CCRT, and CCRT following inducing immunochemotherapy were also included. 1:1 Propensity score matching (PSM) was implemented to balance important baseline characteristics included gender, age, smoking history, histologic type, differentiated degree, cT stage between patients with surgery and radiotherapy. Log-rank test was used to compared progression-free survival (PFS). Results: The median follow-up time of 82 patients with surgery and 114 patients with radiotherapy was 28.1 months and 21.8 months, respectively. In patients with surgery, 29 patients reach complete pathological response (pCR) and 53 patients reached node clearance. After PSM, 74 patients with surgery and 74 patients with radiotherapy showed balanced baseline characteristics. Before PSM, patients with surgery displayed a significant advantage in median PFS (24.6 months vs 21.3 months, p=0.040) but this advantage disappeared after PSM (31.3 months vs 30.8 months, p=0.132). In post-treatment subgroup analyses, patients reached pCR had better PFS than patients with radiotherapy (median PFS not reach vs 30.8 months, p=0.001). In addition, patients reached node clearance also had better PFS than patients with radiotherapy (median PFS not reach vs 30.8 months, p=0.010). In pre-treatment subgroup analyses, surgery did not outperform radiotherapy in male or female patients, smokers or nonsmokers, squamous or non-squamous carcinoma and poorly differentiated carcinoma. In patients with high or moderately differentiated tumors, patients with surgery had better PFS than patients with radiotherapy (median PFS not reach vs 13.2 months, p=0.001). Conclusions: In patients with cN3 NSCLC, surgery after neoadjuvant immunochemotherapy do not transcend ICI with CCRT in PFS. Only patients with high or moderately differentiated tumors, or reached pCR, node clearance after surgery have better PFS than patients with radiotherapy. Prospective clinical is needed to evaluate the benefit of surgery after neoadjuvant immunotherapy for cN3 NSCLC.

Chemotherapy + PD-1/PD-L1 Blockade Should Be the Preferred Option in the Neoadjuvant Therapy of NSCLC

Immune-Related Adverse Events and Outcomes in Patients with Advanced Non–Small Cell Lung Cancer: A Predictive Marker of Efficacy?

Background. The standard treatment for localized non-small cell lung cancer (NSCLC) is surgery. However, for inoperable patients or patients who refuse surgical treatment, radiation therapy in different fractionation regimens remains an alternative to surgery. Traditional radiation therapy does not provide treatment results similar to those after surgical treatment, but the use of stereotactic body radiation therapy (SBRT) changes this paradigm, allowing results comparable to surgical treatment. Purpose. To compare the results of treatment of patients with T1–2N 0M0 stages of NSCLC depending on the treatment performed – surgery, radiation therapy in the traditional fractionation mode, stereotactic radiation therapy, combined treatment. Materials and methods. From 2015 to 2021 on the basis of the Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine, 195 patients with non-small cell lung cancer stages T1–2N 0M0 were treated. 79 patients underwent surgical treatment, 81 patients underwent radiation therapy, and the combined treatment group included 35 patients. The operation was more often performed as a lobectomy (62 people), atypical resection was performed in 17 cases. Traditional radiation therapy was performed in 66 patients, stereotactic radiation therapy in 15 patients. In the combination treatment group, radiotherapy was given after atypical resection. Results. Overall survival (OS), regardless of treatment option, was 102 months. OS rates were high in the surgical and combined treatment groups, while median OS was not reached in the surgery group. In the radiation therapy group, OS was 54 months. Progression-free survival (PFS) was 83 months among all patients. PFS rates are highest with surgical treatment (1-year PFS 96 %), in the radiation therapy group the 1-year PFS was 78 %, in the combined treatment group – 80 %. There was no significant difference in OS and PFS depending on the histological subtype of the tumor. The 1-year OS rates in the radiation therapy (RT) group were comparable: after a radical course of RT in the traditional fractionation regimen – 90 %, after SBRT – 93 %. The 5-year OS rates were significantly different: 41 and 60 %, respectively. In a subgroup analysis of surgical treatment, there was a trend towards increased OS in the atypical resection group compared with lobectomy patients: 5-year OS was 80 and 77 %, respectively. Conclusions. Surgical treatment of stages T1–2N 0M0 non-small cell lung cancer should be the main treatment method. For inoperable patients who refuse surgical treatment, SBRT should be preferred to traditional RT.

Meta-Analysis of EGFR Kinase Inhibitors: Not Always Greater Than the Sum of Its Parts

Elderly patients with early stage non-small cell lung cancer (NSCLC) who undergo surgical resection are at a high risk of treatment-related complications. Stereotactic body radiation therapy (SBRT) is considered an alternative treatment option with a favorable safety profile. Given that prospective comparative data on SBRT and surgical treatments are limited, we compared the 2 treatments for early stage NSCLC in the elderly.We retrospectively collected information from the database at our geriatric institution on patients with clinical stage IA/B NSCLC who were treated with surgery or SBRT. The patients were matched using a propensity score based on gender, age, T stage, tumor location, pulmonary function (forced expiratory volume in 1 second [FEV1]% and FEV1), Charlson comorbidity score, and World Health Organization performance score. We compared locoregional control rate, recurrence-free survival (RFS), overall survival (OS), and cancer-specific survival (CSS) between the 2 treatment cohorts before and after propensity score matching.A total of 106 patients underwent surgery, and 74 received SBRT. Surgical patients were significantly younger (72.6 ± 7.9 vs 82.6 ± 4.1 years, P = 0.000), with a significantly higher rate of adenocarcinoma (P = 0.000), better Eastern Cooperative Oncology Group performance scores (P = 0.039), and better pulmonary function test results (P = 0.034 for predicted FEV1 and P = 0.032 for FEV1). In an unmatched comparison, there were significant differences in locoregional control (P = 0.0012) and RFS (P < 0.001). The 5-year OS was 69% in patients who underwent surgery and 44.6% in patients who underwent SBRT (P = 0.0007). The 5-year CSS was 73.9% in the surgery group and 57.5% in the SBRT group (P = 0.0029). Thirty-five inoperable or marginally operable surgical patients and 35 patients who underwent SBRT were matched to their outcomes in a blinded manner (1:1 ratio, caliper distance = 0.25). In this matched comparison, the follow-up period of this subgroup ranged from 4.2 to 138.1 months, with a median of 58.7 months. Surgery was associated with significantly better locoregional control (P = 0.0191) and RFS (P = 0.0178), whereas no significant differences were found in OS (5-year OS, 67.8% for surgery vs 47.4% for SBRT, P = 0.07) or CSS (67.8% for surgery vs 58.2% for SBRT, P = 0.1816).This retrospective analysis found superior locoregional control rates and RFS after surgery compared with SBRT, but there were no differences in OS or CSS. SBRT is an alternative treatment option to surgery in elderly NSCLC patients who cannot tolerate surgical resection because of medical comorbidities. Our findings support the need to compare the 2 treatments in randomized controlled trials.

8550 Background: Nowadays,immune checkpoint inhibitor (ICI) plus chemotherapy is a standard treatment for non-small cell lung cancer (NSCLC) without targetable oncogene alternations. Recently, ipilimumab plus nivolumab-based therapies (CM227 or CM9LA) are also used as standard treatments for NSCLC. Whether ICI plus chemotherapy (ICI-chemo) or ipilimumab plus nivolumab-based therapy (I-N) is better for patients with NSCLC with PD-L1 tumor proportion score (TPS) 1-49% has not been investigated. Here, we report the results of real-world data in NSCLC patients with PD-L1 TPS 1-49%. Methods: We conducted a multicenter (19 centers in Japan) retrospective cohort study. NSCLC patients with PD-L1 TPS 1-49% who received ICI-chemo or I-N as first-line systemic therapy between January 2018 and March 2022 were eligible. Patients with major epidermal growth factor receptor mutations or anaplastic lymphoma kinase rearrangements were excluded. Results: A total of 401 patients were enrolled: median (range) age 69 (35-90) years; 322 (80.3%) male; ECOG PS 0-1, 372 (92.7%); PS ≥2, 29 (7.3%); 233 (58.1%) adenocarcinoma; PD-L1 TPS 1-24%, 312 (77.8%); 25-49%, 82 (20.4%); 1-49% (details are unknown), 7 (1.8%); ICI-chemo 308 (76.8%); I-N, 93 (23.2%). The median overall survival (OS) was 21.0 months (95%CI, 16.7–27.5) in the ICI-chemo group and 20.0 months (95%CI, 15.1–not reached) in the I-N therapy group, respectively. After propensity score matching, there were no differences in OS and progression-free survival (PFS) between ICI-chemo group (n=92) and I-N group (n=92) (OS: HR, 0.83; 95% CI, 0.54-1.26; p=0.38, PFS: HR, 0.72; 95% CI, 0.52-1.00; p=0.05). Among patients with PD-L1 TPS 25-49%, there was a tendency for better OS in the ICI-chemo group (OS: HR, 0.30; 95% CI, 0.09–0.85, p=0.02). In contrast, among PD-L1 TPS 1-24%, significant difference in OS was not observed. Regarding safety, treatment discontinuation due to adverse events was observed 26.2% in the ICI-chemo group and 41.9% in the I-N group. Treatment related death was seen in 4.5% of the ICI-chemo group and in 3.2% of the I-N group. Pneumonitis was seen in 13.9% of the ICI-chemo group and in 17.6% of the N-I group. Conclusions: In real-world data for NSCLC with PD-L1 TPS 1-49%, there were no significant differences in both OS and PFS between ICI-chemo group and I-N group. Toxicity discontinuation rate was higher in I-N group. Based on the subgroup-analysis results, ICI-chemo might be better for NSCLC with PD-L1 TPS 25-49%. Clinical trial information: UMIN000016441.

Introduction In patients with non-small cell lung cancer (NSCLC) who present with multiple pulmonary nodules, it is often difficult to distinguish metastatic disease from synchronous primary lung cancers (SPLC). We sought to evaluate clinical outcomes after stereotactic body radiotherapy (SBRT) alone to synchronous primary lesions. Material and methods Patients with synchronous AJCC 8th Edition Stage IA-IIA NSCLC and treated with stereotactic body radiation therapy (SBRT) to all lesions between 2009–2018 were reviewed. SPLC was defined as patients having received two courses of SBRT within 180 days for treatment of separate early stage tumors. In total, 36 patients with 73 lesions were included. Overall survival (OS), progression-free survival (PFS), cumulative incidence of local failure (LF), and regional/distant failure (R/DF) were estimated and compared with a control cohort of solitary early stage NSCLC patients. Results Median PFS was 38.8 months (95% CI 14.3-not reached [NR]); 3-year PFS rates were 50.6% (35.6–72.1). Median OS was 45.9 months (95% CI: 35.9-NR); 3-year OS was 63.0% (47.4–83.8). Three-year cumulative incidence of LF and R/DF was 6.6% (3.7–13.9) and 35.7% (19.3–52.1), respectively. Patients with SPLC were compared to a control group (n = 272) of patients treated for a solitary early stage NSCLC. There was no statistically significant difference in PFS (p = .91) or OS (p = .43). Evaluation of the patterns of failure showed a trend for worse cumulative incidence of R/DF in SPLC patients as compared to solitary early stage NSCLC (p = .06). Conclusion SBRT alone to multiple lung tumors with SPLC results in comparable PFS, OS, and LF rates to a cohort of patients treated for solitary early stage NSCLC. Those with SPLC had non-significantly higher R/DF. Patients with SPLC should be followed closely for failure and possible salvage therapy.

BackgroundWe hypothesized that significant tumor volume reduction (TVR) occurs over the course of stereotactic body radiotherapy (SBRT) for early stage non-small cell lung cancer (NSCLC), and that TVR correlates with clinical outcomes.MethodsWe conducted a retrospective review of patients treated with SBRT for early stage NSCLC across two academic centers. For each patient, we contoured the tumor volume (TV) on cone beam computed tomography (CBCT) images obtained before each treatment fraction. We then calculated TVR based on the TV from the first and last days of treatment. We used log-rank tests to quantify differences in overall survival (OS), progression-free survival (PFS) and recurrence based on TVR.ResultsData from 69 patients and a total of 73 treated tumors were analyzed. The median follow-up for survivors was 51.8 months (range, 6.9 to 80.0 months). The median TVR for the cohort was 10.1% (range, −5.7% to 43.5%). There was no significant difference in either OS (median 33.4 vs. 29.1 months, P=0.79) or PFS (median 26.3 vs. 12.3 months, P=0.43) for those with high TVRs (≥10.1%) vs. low TVRs (<10.1%), respectively. There was a trend toward superior 2-year PFS in the high TVR group (52.2% vs. 36.7%, P=0.062), but this effect diminished on longer follow-up (4-year PFS 31.9% vs. 26.7%, P=0.15). No associations were observed between TVR and local, regional or distant recurrence.ConclusionsWe were not able to demonstrate that TVR is a reliable predictive imaging marker for stage I/II NSCLC treated with SBRT. Future studies with larger sample sizes are needed to clarify a potential relationship between TVR and early outcomes.

Survival and recurrence rates following SBRT or surgery in medically operable Stage I NSCLC

Brief Report: First-line Pembrolizumab in Metastatic Non-Small Cell Lung Cancer Habouring MET Exon 14 Skipping Mutation and PD-L1 ≥50% (GFPC 01-20 Study)