IB Non-small Cell Lung Cancer Research Articles

Optimizing the fairness of survival prediction models for racial/ethnic subgroups: A study on predicting post-operative survival in stage IA and IB non-small cell lung cancer.

380 Background: The recent surge of utilizing machine learning (ML) to develop prediction models for clinical decision-making aids is promising. However, these models can demonstrate racial bias due to inequities in real-world training data. In lung cancer, multiple models have been developed to predict prognosis, but none have been optimized to mitigate bias in performance among racial/ethnic subgroups. We developed a ML model to predict five-year survival in Stage 1A-1B non-small cell lung cancer (NSCLC), ensuring fairness on race. Methods: In the National Cancer Database, we identified patients with histopathologically confirmed stage 1A -1B NSCLC who underwent curative intent lobectomy from 2004 – 2017. We split the study cohort into a training and test sets (70%/30%). We trained and compared various ML models to predict 5-year overall survival. Patient demographic, clinical, and disease characteristics were used as input features for the models. To evaluate model fairness, we used the equalized odds ratio (eOR), which compares the true positive and false positive rates across groups; an eOR value of 1 represents equivalent rates across racial groups. We utilized 3 approaches to mitigate model bias and optimize for fairness of the best “naïve” model: grid search, threshold optimizer, and the exponentiated gradient methods. We evaluated model performance before and after bias mitigation using the area under the curve (AUC). Results: 124,298 patients fit our inclusion/exclusion criteria; 87% of patients were White, 8% were Black/African American, 3% Hispanic, and 2% Asian. Eighty percent of patients were diagnosed with stage 1A cancer; 20% had stage 1B cancer. The best naïve ML model, not optimized for fairness on race, had an eOR of 0.25 with an AUC of 0.66 (95% CI 0.65-0.66) overall. This model demonstrated an AUC of 0.65 (0.65-0.66) among white patients, 0.64 (0.62-0.66) among Black patients, 0.64 (0.60-0.68) among Asian patients, and 0.71 (0.68-0.74) among Hispanic patients. The threshold optimizer bias mitigation strategy improved fairness the most while maintaining similar overall performance of AUC 0.65 (0.64-0.66). With this strategy the eOR improved to 0.83 while AUC remained relatively stable across racial subgroups. Conclusions: We developed a ML model to predict 5-year survival in patients undergoing surgery for stage IA-IB NSCLC and employed model bias mitigation strategies that significantly improved model fairness, without diminishing overall performance. These strategies should be considered when developing prediction models for clinical decision making to avoid perpetuating disparities in care due to algorithm bias. Model performance metrics. Equalized Odds Ratio True Positive Rate False Positive Rate AUC Naive model 0.25 0.61 0.30 0.66 Threshold optimizer mitigated model 0.83 0.62 0.32 0.65

Histopathologic pattern and molecular risk stratification are associated with prognosis in patients with stage IB lung adenocarcinoma.

The benefit of adjuvant therapy remains controversial in completely resected (R0) stage IB non-small cell lung cancer (NCLSC) patients. In this study, we aimed to explore potential prognostic factors in stage IB NSCLC patients. This study included 215 patients with R0 stage IB lung adenocarcinoma (LUAD) (tumor size: 3-4 cm). DNA sequencing was performed with surgical samples of 126 patients using a panel of 9 driver genes. The molecular risk stratification was assessed by a 14-gene quantitative polymerase chain reaction assay. Among the 215 patients, 67.9% had micropapillary/solid (MIP/SOL)-predominant tumors. Epidermal growth factor receptor (EGFR) mutations were detected in 75 of 126 patients (59.5%). MIP/SOL tumors harbored less common EGFR mutations than the other histologic patterns (50.6% vs. 79.5%, P=0.003). Molecular risk stratification was successfully assessed in 99 patients, of whom 37.4%, 26.3%, and 36.4% were high, intermediate, and low risk, respectively. The MIP/SOL pattern was associated with shorter disease-free survival (DFS) [hazard ratio (HR) =2.16, 95% confidence interval: 1.28-3.67; P=0.01]. The molecular high-risk patients had shorter DFS than the low- (HR =2.93, P=0.01) and intermediate-risk patients (HR =2.35, P=0.06). The prognostic value of molecular risk stratification was also significant in the MIP/SOL subset (median DFS high-risk: 45 months, low and intermediate risk: not reached; P=0.03). Our study showed that both the MIP/SOL pattern and molecular high-risk category were adverse prognostic factors in stage IB NSCLC patients. Our results suggest that combining histologic classification and molecular risk stratification may help to identify the subset of patients with poor prognosis.

SF6 is a useful expander for post-pneumonectomy syndrome in the long-term course: a case report

BackgroundPost-pneumonectomy syndrome (PPS) is a rare but serious condition that can occur after pneumonectomy. It is characterized by a mediastinal shift towards the vacated hemithorax, which can potentially lead to respiratory failure. The management of PPS poses a clinical challenge, especially in the context of the limited availability of certain therapeutic devices due to regulatory restrictions in Japan.Case presentationA 36-year-old female with stage IB non-small cell lung cancer underwent left pneumonectomy. Approximately 2 years later, she developed dyspnea. After consulting with our hospital, subsequent imaging revealed an extreme mediastinal shift causing bronchial obstruction. Emergency thoracotomy and subsequent sulfur hexafluoride (SF6) injections were successfully used to manage her condition. Over the course of follow-up, the interval between SF6 injections was extended from 3 to 11 months, indicating an improvement in the intrathoracic condition.ConclusionsThis case illustrates the efficacy of SF6 gas in treating PPS and in reducing the frequency of medical interventions. SF6 gas administration is safe and effective for the treatment of patients with PPS.

Long-term survival outcomes and quality of life of image-guided proton therapy for operable stage I non-small cell lung cancer: A phase 2 study

Background and purposeThis study evaluated long-term efficacy, safety, and changes in quality of life (QOL) of patients after image-guided proton therapy (IGPT) for operable stage I non-small cell lung cancer (NSCLC). Materials and methodsThis single-institutional prospective phase 2 study enrolled patients with operable histologically confirmed stage IA or IB NSCLC (7th edition of UICC). The prescribed dose was 66 Gy relative biological effectiveness equivalents (GyRBE) in 10 fractions for peripheral lesions, or 72.6 GyRBE in 22 fractions for central lesions. The primary endpoint was the 3-year overall survival (OS). The secondary endpoints included disease control, toxicity, and changes in QOL score. ResultsWe enrolled 43 patients (median age: 68 years; range, 47–79 years) between July 2013 to January 2021, of whom 41 (95 %) had peripheral lesions and 27 (63 %) were stage IA. OS, local control, and progression-free survival rates were 95 % (95 % CI: 83–99), 95 % (82–99), and 86 % (72–94), respectively, at 3 years, and 83 % (66–92), 95 % (82–99), and 77 % (60–88), respectively, at 7 years. Four patients (9 %) developed grade 2, and one patient (2 %) developed grade 3 radiation pneumonitis. No other grade 3 or higher adverse events were observed. In the QOL analysis, global QOL remained favorable; however, approximately 40 % of patients reported dyspnea at 3 and 24 months. ConclusionOur findings suggest that IGPT provides effective disease control and survival in operable stage I NSCLC, particularly for peripheral lesions. Moreover, toxicity associated with IGPT was minimal, and patients reported favorable QOL.

Abstract CT281: The phase 3 INTerpath-002 study design: Individualized neoantigen therapy (INT) V940 (mRNA-4157) plus pembrolizumab vs placebo plus pembrolizumab for resected early-stage non-small-cell lung cancer (NSCLC)

Abstract Background: Pembrolizumab (pembro; anti-PD-1) is indicated as adjuvant monotherapy following resection and adjuvant chemotherapy in patients (pts) with stage IB (T2a ≥4 cm), II, or IIIA NSCLC (per AJCC v7). However, many pts experience disease recurrence, and have limited treatment options available. V940 (mRNA-4157) is a novel individualized neoantigen therapy that encodes up to 34 neoantigens that is specifically tailored and manufactured for each pt derived from their tumor. V940 as monotherapy and in combination with pembro has shown preliminary antitumor activity in the phase 1 KEYNOTE-603 study in several solid tumor types, including NSCLC. Additionally, in pts with completely resected, high-risk stage IIIB/C/D and IV cutaneous melanoma in the KEYNOTE-942 primary analysis, V940 plus pembro demonstrated significant improvements in recurrence-free survival (HR, 0.561 [95% CI, 0.309-1.017]; P = 0.0266) and distant metastasis-free survival (HR, 0.347 [95% CI, 0.145-0.828]; P = 0.0063) vs pembro alone. Here we present the design of the phase 3, randomized, double-blind INTerpath-002 study (NCT06077760) of adjuvant V940 plus pembro vs placebo plus pembro in pts with completely resected and chemotherapy-treated stage II-IIIB (N2) NSCLC (AJCC v8). Methods: Eligible pts aged ≥18 years with completely resected stage II, IIIA, or IIIB (N2) squamous or nonsquamous NSCLC (per AJCC v8.0) where EGFR-directed therapy is not indicated as primary therapy (ie, absence of sensitizing EGFR mutations e.g. DEL19 or L858R), who have received 1-4 doses of adjuvant platinum-doublet chemotherapy, have ECOG PS 0 or 1, and have available tumor tissue for next-generation sequencing and PD-L1 testing will be enrolled. Pts must not have received previous neoadjuvant therapy for NSCLC and must not have received or be candidates for adjuvant radiotherapy. Pts will be randomized 1:1 to receive V940 1 mg IM or placebo Q3W for up to 9 doses plus pembro 400 mg IV Q6W for up to 9 cycles or until disease recurrence, pt withdrawal, unacceptable toxicity, or an additional malignancy requiring treatment. Randomization will be stratified by histology (squamous vs nonsquamous), PD-L1 TPS (<1% vs 1%-49% vs ≥50%), disease stage (II vs III), and geographic location (North America/Western Europe/Australia vs rest of world). The primary endpoint is disease-free survival per investigator review. Secondary endpoints include distant metastasis-free survival per investigator assessment, OS, lung cancer‒specific survival, patient-reported outcomes, and safety. Tumor imaging will occur at baseline, every 12 wk until wk 48, every 24 wk through year 3, and every 48 wk thereafter. Enrollment began in October 2023 and is ongoing globally (NCT06077760). Citation Format: Jonathan D. Spicer, Santosh M. Nair, Adnan Khattak, Jay M. Lee, Michelle Brown, Robert S. Meehan, Nazly Shariati, Xuan Deng, Ayman Samkari, Jamie E. Chaft. The phase 3 INTerpath-002 study design: Individualized neoantigen therapy (INT) V940 (mRNA-4157) plus pembrolizumab vs placebo plus pembrolizumab for resected early-stage non-small-cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT281.

Impact of adjuvant chemotherapy on patients with stage IB non-small cell lung cancer with visceral pleural invasion.

Adjuvant chemotherapy has reduced the risk of recurrence and death in stage IB non-small cell lung cancer (NSCLC) with high-risk factors; however, the impact of visceral pleural invasion (VPI) on outcomes in stage IB NSCLC treated with adjuvant chemotherapy remains controversial. The aim of this study was to explore the clinical and prognostic significance of adjuvant chemotherapy for stage IB (1-4 cm) NSCLC with VPI. This retrospective study included 251 patients admitted between January 2008 and May 2018 from four hospitals who underwent complete resection for Tumor-Node-Metastasis (TNM) 8th edition stage IB NSCLC with VPI. The relationship between adjuvant chemotherapy and overall survival (OS) or recurrence-free survival (RFS) was analyzed using the Kaplan-Meier method and Cox proportional hazards model. Of 251 patients with stage IB NSCLC with VPI, 122 (48.6%) received adjuvant chemotherapy after surgical resection and 129 (51.4%) were placed under observation. Multivariable analysis showed that adjuvant chemotherapy was an independent predictor of RFS [adjusted hazard ratio (aHR), 0.57; 95% confidence interval (CI): 0.33-0.96; P=0.036]. A micropapillary pattern (aHR, 2.46; 95% CI: 1.33-4.55; P=0.004) and lymphovascular invasion (aHR, 2.86; 95% CI: 1.49-5.48; P=0.002) were associated with a higher risk of recurrence. Multivariable analysis also showed that adjuvant chemotherapy was an independent predictor of OS (aHR, 0.22; 95% CI: 0.09-0.58; P=0.002). In a subgroup analysis of patients with a tumor size of 1-3 cm, adjuvant chemotherapy was associated with improved RFS and OS, and this association was maintained even when patients with VPI had additional risk factors. Our study shows that adjuvant chemotherapy is appropriate for patients with stage IB (1-4 cm) NSCLC with VPI, and even those with smaller tumors (1-3 cm).

Diagnosis, treatment, and prognosis of stage IB non-small cell lung cancer with visceral pleural invasion.

With the increasing implementation of early lung cancer screening and the increasing emphasis on physical examinations, the early-stage lung cancer detection rate continues to rise. Visceral pleural invasion (VPI), which denotes the tumor's breach of the elastic layer or reaching the surface of the visceral pleura, stands as a pivotal factor that impacts the prognosis of patients with non-small cell lung cancer (NSCLC) and directly influences the pathological staging of early-stage cases. According to the latest 9th edition of the TNM staging system for NSCLC, even when the tumor diameter is less than 3 cm, the final T stage remains T2a if VPI is present. There is considerable controversy within the guidelines regarding treatment options for stage IB NSCLC, especially among patients exhibiting VPI. Moreover, the precise determination of VPI is important in guiding treatment selection and prognostic evaluation in individuals with NSCLC. This article aims to provide a comprehensive review of the current status and advancements in studies pertaining to stage IB NSCLC accompanied by VPI.

Meta-analysis of the efficacy of postoperative adjuvant chemotherapy for stage IB non-small cell lung cancer.

Many clinical trials have shown that postoperative adjuvant chemotherapy can provide a survival benefit for patients with stage IB non-small cell lung cancer. However, whether adjuvant chemotherapy should be routinely given after surgery remains controversial. Therefore, we performed a meta-analysis to investigate the efficacy of adjuvant chemotherapy versus surgery alone for stage IB non-small cell lung cancer (NSCLC). Relevant retrospective studies or randomized controlled trial comparing the efficacy of postoperative adjuvant chemotherapy versus observation on the survival outcomes of NSCLC patients up to October 30, 2023 were searched in PubMed, Web of Science, EMBASE, Cochrane Library, VIP database, Wanfang database, and China National Knowledge Internet database. Patient survival data, population characteristics, and other relevant information were extracted, and data were analyzed using Review Manager 5.4. The primary endpoints included overall survival, disease-free survival, and recurrence-free survival. A total of 13 randomized controlled trials or cohort studies including 19,442 patients were included. The results of the meta-analysis showed that postoperative adjuvant chemotherapy in patients with stage IB NSCLC had better overall survival (odds ratio [OR] = 1.25, 95% confidence interval [CI] 1.19-1.31, P < .00001) and disease-free survival or recurrence-free survival (OR = 1.57, 95% CI 1.3-1.9, P < .00001) compared with observation; and the 4-year survival rate of patients who received postoperative adjuvant chemotherapy was better than the observation group (OR = 1.52, 95% CI 1.05-2.18, P = .03); and the 8-year survival rate of patients receiving postoperative adjuvant chemotherapy (OR = 1.5, 95% CI 0.94-2.4, P = .09) was comparable to the observation group. Receiving postoperative adjuvant chemotherapy improved people's survival and prolonged disease-free survival and recurrence-free survival in patients with stage IB non-small cell lung cancer compared with surgery alone.

Influence of adjuvant chemotherapy on survival for patients with completely resected high-risk stage IB NSCLC

BackgroundThe use of adjuvant chemotherapy (ACT) in completely resected stage IB NSCLC is still controversial. This study aims to investigate the efficacy of ACT in pathological stage IB non-small cell lung cancer (NSCLC) with high risk factors.MethodsPatients with pT2aN0M0 stage IB NSCLC who underwent complete resection from 2013 to 2017 were retrospectively analyzed. Univariate and multivariable logistic regression analysis was used to assess potential independent risk factors associated with poor prognosis. To compare survival between patients who received ACT and those who did not.ResultsIn univariate and multivariate analyses, adenocarcinomas with predominantly micropapillary (MIP) and solid patterns (SOL), poorly differentiated squamous cell carcinoma (SCC), number of lymph nodes dissected less than 16 and tumor size larger than 36 mm were identified as high-risk factors for recurrence. In patients with high risk factors for recurrence, ACT resulted in significantly longer DFS (HR, 0.4689, 95%CI, 1.193–3.818; p = 0.0108) and OS (HR, 0.4696, 95%CI, 0.6578–6.895; p = 0.2073), although OS failed to reach statistically significance. After propensity score matching (PSM), 67 pairs of patients were 1:1 matched in the two groups and all baseline characteristics were well balanced. The results also demonstrated that ACT was associated with improved DFS (HR, 0.4776, 95%CI, 0.9779–4.484; p = 0.0440) while OS was not significantly different (92.5% vs. 91.0%; HR, 0.6167, 95%CI, 0.1688–2.038; p = 0.7458). In patients with low-risk factors for recurrence, DFS (HR, 0.4831, 95%CI, 0.03025-7.715; p = 0.6068) and OS (HR, 0.969, 95%CI, 0.08364-11.21; p = 0.9794) was not significantly different between those who received ACT and those who did not.ConclusionIn patients with completely resected stage IB NSCLC, ACT can improve survival in patients with high risk for recurrence. Further large multicenter studies are needed to confirm these findings.

MO62-4 Evaluation of the significance of subcarinal lymph node dissection in stage IB non-small cell lung cancer

MO62-4 Evaluation of the significance of subcarinal lymph node dissection in stage IB non-small cell lung cancer

Diagnostic Workup, Treatment Patterns, and Clinical Outcomes in Early-Stage IB-IIIA Non-Small-Cell Lung Cancer Patients in Denmark.

Despite recent improvements in early-stage non-small-cell lung cancer (NSCLC), disease relapse remains challenging. Moreover, real-world evidence on long-term follow-up of disease-free survival (DFS) and recurrence patterns in a large, unselected cohort of early-stage NSCLC patients is lacking. This cohort study aimed to assess clinical characteristics, diagnostic workup, treatment, survival, and risk of disease relapse among early-stage NSCLC patients. Adult patients with stage IB, II, or IIIA NSCLC diagnosed and/or treated at Aarhus University Hospital in Denmark from January 2010 to December 2020 were included and followed-up until May 2021. Comprehensive clinical data were collected from electronic medical records of eligible patients and linked to Danish register data. The study population comprised 1341 early-stage NSCLC patients: 22%, 40%, and 38% were diagnosed with stage IB, II, and IIIA disease, respectively. In total, 42% of patients were tested for epidermal growth factor receptor (EGFR), of whom 10% were EGFR-mutation-positive (EGFRm+). Half of all patients received surgery, and nine percent of patients received stereotactic body radiation therapy (SBRT). Disease-free survival 5 years post-diagnosis was 49%, 42%, and 22% for stage IB, II, and stage IIIA patients, respectively. DFS improved over time both for patients treated with surgery and SBRT. However, disease relapse remained a challenge, with approximately 40% of stage IIIA having relapsed 3 years post-diagnosis. This study contributes important knowledge that puts clinical trials on new perioperative treatment modalities for early-stage NSCLC patients into perspective. Our findings cover an essential evidence gap on real-world DFS and recurrence dynamics, confirming that despite an improvement in DFS over time and across different treatment modalities, disease relapse remains a monumental challenge. Therefore, better treatment strategies are needed.

Clinical efficacy and safety of adjuvant EGFR-TKIs for resected stage IB lung adenocarcinoma: A real-world study based on propensity score matching.

Adjuvant therapy for stage IB non-small cell lung cancer remains debatable. In this real-world study, we evaluate the efficacy and safety of adjuvant epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for resected stage IB lung adenocarcinoma. This real-world study recruited 249 patients diagnosed with stage IB disease after surgical resection between January 2013 and September 2021. Sixty-six (26.5%) patients received adjuvant targeted therapy (TKIs group), and 183 (73.5%) were enrolled in the clinical observation (CO) group. Propensity scores were matched to minimize the observed confounder effects between the two groups, and 59 patient pairs were matched. The primary endpoint was disease-free survival (DFS). In the TKI group, 38 (64.4%) patients chose to receive icotinib, 27.1% (16/59) received gefitinib, and 5 patients (8.5%) chose osimertinib. The median follow-up time was 30.8 months (range: 7-107 months). Two (3.4%) patients in the TKI group and 10 (16.9%) in the CO group experienced disease relapse. The 3-year DFS rates were 98.3% in the TKI group and 83.0% in the CO group (HR: 0.10; 95% CI: 0.01-0.78; p = 0.008). DFS differences were found in the entire cohort (p = 0.005) and the matched cohort (p = 0.024) between the two groups. Multivariate analysis showed that adjuvant EGFR-TKIs was an independent factor for DFS (HR: 0.211; 95% CI: 0.045-0.979; p = 0.047), along with poor cell differentiation (HR: 5.256; 95% CI: 1.648-16.769; p = 0.005), and spread through air spaces (HR: 5.612; 95% CI: 1.137-27.700; p = 0.034). None of the patients discontinued EGFR-TKIs owing to the low occurrence rate of treatment-related serious adverse events. Adjuvant EGFR-TKIs could significantly improve DFS among patients with stage IB lung adenocarcinoma compared with CO, with a safe and tolerable profile.

Prognostic Factors for Survival of Stage IB Non-small Cell Lung Cancer Patients: A 10-Year Follow-Up Retrospective Study.

This study aimed to determine the prognostic factors for the long-term outcome of stage IB non-small cell lung cancer (NSCLC). Surgically resected patients with stage IB NSCLC diagnosed (based on TNM 8th edition) between April 2008 and December 2013 were retrospectively reviewed. The prognosis and possible risk factors among the stage IB NSCLC patients were evaluated. Of the 349 patients identified for the study, 80 (22.9%) received post-surgery adjuvant chemotherapy (ACT). The median follow-up time after surgery was 123.3 months. The 10-year overall survival (OS) rate was 69.6%, and the 10-year recurrence-free survival (RFS) rate was 62.8%. The patients in this cohort were divided into three groups (T1 with visceral pleural invasion [VPI], T2a without VPI, and T2a with VPI), and no significant differences in OS or RFS were found among the groups. Furthermore, survival analysis indicated that the absence of ground-glass opacity (GGO) components portends an adverse long-term OS and RFS. In a subgroup of patients with solid nodules, age older than 65 years (hazard ratio [HR] 1.987; 95% confidence interval [CI] 1.312-3.010; p = 0.001) and ACT (HR 0.392; 95% CI 0.225-0.684; p < 0.001) were independent prognostic factors for OS, whereas lymphovascular invasion (HR 1.792; 95% CI 0.995-3.227; p = 0.052) should be considered as an independent unfavorable prognostic factor for RFS. As an upstaging factor, VPI did not further stratify prognosis for the stage IB patients in our cohort. The presence of GGO components had a notable impact on a favorable prognosis in stage IB NSCLCs.

Lobe-specific analysis of perioperative chemotherapy for non-small cell lung cancer patients.

Perioperative cisplatin-based chemotherapy decreases the risk of death over surgery alone and is a standard of care. Here, we examined perioperative chemotherapy indications for stage IB-III non-small cell lung cancer (NSCLC) patients according to lobe-specific analysis. Resectable NSCLC patients with stage IB-III who received perioperative chemotherapy with and without radiotherapy after lung resection were identified from the SEER database. Propensity score matching (PSM) analysis was performed to reduce the inherent bias of retrospective studies. The Kaplan-Meier method and log-rank tests were used to assess the differences in overall survival (OS). The study enrolled 23,844 patients before PSM. The perioperative chemotherapy group had better OS than the nonperioperative chemotherapy group in stage IB-III NSCLC patients before and after PSM. However, subgroup analysis according to stage demonstrated that perioperative chemotherapy did not markedly benefit patients with stage IB. Furthermore, lobar subgroup analysis did not show survival advantages in primary tumors located in either the right middle lobe in stages II and III NSCLC or the right lower lobe in stage III NSCLC. Lobe-specific perioperative chemotherapy is recommended in NSCLC patients. For stage IB NSCLC, right middle lobe NSCLC from stage IB-III and right lower lobe NSCLC from stage III, perioperative chemotherapy might not confer survival benefits.

Evaluation of the significance of subcarinal lymph node dissection in stage IB non‑small cell lung cancer.

Lymph node dissection is used to treat early-stage lung cancer. The present study aimed to investigate if resecting the subcarinal lymph nodes affects prognosis of patients with stage IB non-small cell lung cancer (NSCLC). A total of 597 patients with stage IB NSCLC who underwent lung cancer surgery at Sun Yat-Sen University Cancer Center from January 1999 to December 2009 were included in the present study. The potential prognostic factors were evaluated using the Cox proportional hazard regression model. A total of 252 cases were obtained following propensity score matching (PSM). To compare overall survival (OS) and recurrence-free survival (RFS), Kaplan-Meier method and log-rank test were used. Among the 597 cases included, 185 did not undergo subcarinal lymph node resection, whereas 412 did. There were statistically significant differences between the two groups in terms of bronchial invasion, number of resected lymph node stations and resected lymph node numbers (P<0.05). Age, family history of cancer and the number of resected lymph nodes were prognostic factors for OS, whereas age and the number of resected lymph nodes were prognostic factors for RFS (P<0.05). Resection of subcarinal lymph nodes was not associated with OS and RFS. After PSM, survival analysis was recalculated using the Kaplan-Meier method and log-rank test; subcarinal lymph node resection was not statistically associated with OS and RFS. (P>0.05). For stage IB NSCLC, there was no statistically significant association between subcarinal lymph node resection and OS and RFS. Subcarinal lymph node resection in surgery of stage IB NSCLC may be considered optional.

Prognostic value of TLR from FDG PET/CT in patients with margin-negative stage IB and IIA non-small cell lung cancer.

To evaluate the prognostic value of TLR from PET/CT in patients with resection margin-negative stage IB and IIA non-small cell lung cancer (NSCLC) and compare high-risk factors necessitating adjuvant treatment (AT). Consecutive FDG PET/CT scans performed for the initial staging of NSCLC stage IB and IIA were retrospectively reviewed. The maximum standardized uptake value (SUVmax) of the primary tumor and mean SUV of the liver were acquired. The tumor-to-liver SUV ratio (TLR) was also calculated. Charts were reviewed for basic patient characteristics and high-risk factors for considering AT (poor differentiation, visceral pleura invasion, vascular invasion, tumors > 4cm, and wedge resection). Statistical analysis was performed using Cox regression analysis and the Kaplan-Meier method. Of the 112 patients included, 15 (13.4%) died, with a median overall survival (OS) of 43.8months. Twenty-two patients (19.6%) exhibited recurrence, with median disease-free survival (DFS) of 36.0months. In univariable analysis, pathology, poor differentiation, and TLR were associated with shorter DFS and OS. In multivariable analysis, TLR (hazard ratio [HR] = 1.263, p = 0.008) and differentiation (HR = 3.087, p = 0.012) were associated with shorter DFS. Also, TLR (HR = 1.422, p < 0.001) was associated with shorter OS. TLR from FDG PET/CT was an independent prognostic factor for recurrence and survival. PET parameters constitute risk factors for consideration in the decision-making for AT in margin-negative stage IB and IIA NSCLC. In this study, TLR from FDG PET/CT was an independent prognostic factor in stage IB-IIA non-small cell cancer patients. Although additional validation studies are warranted, TLR has the potential to be used to determine the need for adjuvant therapy. • High TLR is an independent poor prognostic factor in stage IB-IIA NSCLC. • Adjuvant treatment should be considered in patients with high TLR following complete tumor resection.

Surgically Treated pT2aN0M0 (Stage IB) Non-Small Cell Lung Cancer: A 20-Year Single-Center Retrospective Study

Introduction The suitability of adjuvant therapy (AT) in patients with stage IB non-small cell lung cancer (NSCLC) is still under debate considering the cost-benefit ratio between improvement in survival and side effects. We retrospectively evaluated survival and incidence of recurrence in radically resected stage IB NSCLC, to determine whether AT could significantly improve prognosis. Methods Between 1998 and 2020, 4692 consecutive patients underwent lobectomy and systematic lymphadenectomy for NSCLC. Two hundred nineteen patients were pathological T2aN0M0 (>3 and ≤4 cm) NSCLC 8th TNM. None received preoperative or AT. Overall survival (OS), cancer specific survival (CSS) and the cumulative incidence of relapse were plotted and log-rank or Gray's tests were used to assess the difference in outcome between groups. Results The most frequent histology was adenocarcinoma (66.7%). Median OS was 146 months. The 5-, 10-, and 15-year OS rates were 79%, 60%, and 47%, whereas the 5-, 10-, and 15-year CSS were 88%, 85%, and 83%, respectively. OS was significantly related to age (p < 0.001) and cardiovascular comorbidities (p = 0.04), whereas number of LNs removed was an independent prognostic factor of CSS (p = 0.02). Cumulative incidence of relapse at 5-, 10-, and 15-year were 23%, 31%, and 32%, respectively, and significantly related to the number of LNs removed (p = 0.01). Patients with more than 20 LNs removed and clinical stage I had a significantly lower relapse (p = 0.02). Conclusions Excellent CSS, up to 83% at 15-year, and relatively low risk of recurrence for stage IB NSCLC (8th TNM) patients suggested that AT for those patients could be reserved only for very selected high-risk cases.

Adjuvant icotinib versus observation in patients with completely resected EGFR-mutated stage IB NSCLC (GASTO1003, CORIN): a randomised, open-label, phase 2 trial.

This phase 2 trial aimed to compare adjuvant icotinib with observation in patients with epidermal growth factor receptor (EGFR) mutation-positive resected stage IB non-small cell lung cancer (NSCLC). We performed a randomised, open-label, phase 2 trial from May 1, 2015 to December 29, 2020at Sun Yat-sen University Cancer Center in China. Patients with completely resected, EGFR-mutant, stage IB (the 7th edition of TNM staging) NSCLC without adjuvant chemotherapy were randomised (1:1) to receive adjuvant therapy with icotinib (125mg, three times daily) for 12 months or to undergo observation until disease progression or intolerable toxicity occurred. The primary endpoint was 3-year disease-free survival (DFS). CORIN (GASTO1003) was registered with Clinicaltrials.gov, with the number NCT02264210. A total of 128 patients were randomised, with 63 patients in the icotinib group and 65 patients in the observation group. The median duration of follow-up was 39.9 months. The three-year DFS was significantly higher in the icotinib group (96.1%, 95% confidence interval [CI], 91.3-99.9) than in the observation group (84.0%, 95% CI, 75.1-92.9; P=0.041). The DFS was significantly longer in the icotinib group than in the observation group, with a hazard ratio (HR) of 0.23 (95% CI, 0.07-0.81; P=0.013). The OS data were immature, with three deaths in the observation arm. In the icotinib group, adverse events (AEs) of any grade were reported in 49 patients (77.8%), and grade 3 or greater AEs occurred in four patients (6.3%). No treatment-related deaths occurred. Our findings suggested that adjuvant icotinib improved the 3-year DFS in patients with completely resected EGFR-mutated stage IB NSCLC with a manageable safety profile. This study was sponsored by Betta Pharmaceutical Co., Ltd.

Should adjuvant treatment be offered to patients with stage IB non-small cell lung cancer?

Should adjuvant treatment be offered to patients with stage IB non-small cell lung cancer?

Adjuvant chemotherapy or immunotherapy for completely resected stage IB non-small cell lung cancer: still a grey zone?

Adjuvant chemotherapy or immunotherapy for completely resected stage IB non-small cell lung cancer: still a grey zone?